Robot-assisted rehabilitation of people with breast cancer developing upper limb lymphedema: protocol of a randomized controlled trial with a 6-month follow­up.

Upper limb lymphedema (ULLy) is an external (and/or internal) manifestation of lymphatic system insufficiency and deranged lymph transport for more than 3 months and frequently affects people as a consequence of breast cancer (BC). ULLy is often underestimated despite diminished motor skills, mood, and cognitive-behavioral complaints negatively condition the health-related quality of life (HRQoL) of persons. BC can also metastasize to the jawbone, further impacting on the HRQoL. In time, the implementation of robot-assisted rehabilitation (RR) for neurological diseases has grown to improve HRQoL and pain. This study aims to evaluate the effectiveness of a RR program in the treatment of individuals who develop an ULLy; as a further analysis, the study will assess the effectiveness of the same program in people with jawbone metastases from BC who will also develop ULLy. A randomized, parallel-group superiority-controlled trial will be conducted. 44 participants will be randomly allocated to either the experimental (receiving a RR program) or the control group (regular rehabilitation). Both groups will follow individual-based programs three times a week for 10 weeks. The main outcome measure will be the Lymphedema Quality of Life Questionnaire. Secondary outcomes will be a pain intensity numerical rating scale and the Cranio-Facial Pain Disability Inventory. Evaluations are before and after training and 6 months later. Findings may provide evidence on the effectiveness of a RR program on inducing improvements in the HRQoL and pain of individuals with ULLy due to BC. People with ULLy and jawbone metastases from BC are expected for similar or higher improvements as per the same comparisons above. This trial might contribute towards defining guidelines for good clinical rehabilitation routines and might be used as a basis for health authorities' endorsements.Trial registration OSF REGISTRIES, osf-registrations-jz7ax-v1 . Registered on 26 June 2023.

Responsiveness and minimal important change of the Pain Catastrophizing Scale in people with chronic low back pain undergoing multidisciplinary rehabilitation.

BACKGROUND: The Pain Catastrophizing Scale (PCS), a widely used tool to assess catastrophizing related to spinal disorders, shows valid psychometric properties in general but the minimal important change (MIC) is still not determined. AIM: The aim of this study was to assess responsiveness and MIC of the PCS in individuals with chronic low back pain (LBP) undergoing multidisciplinary rehabilitation. DESIGN: Prospective observational study. SETTING: The setting was outpatient rehabilitation hospital. POPULATION: Two hundred and five patients with chronic LBP. METHODS: Before and after an 8-week multidisciplinary rehabilitation program, 205 patients completed the Italian version of the PCS (PCS-I). We calculated the PCS-I responsiveness by distribution-based methods (effect size [ES], standardized response mean [SRM], and minimum detectable change [MDC]) and anchor-based methods [receiver operating characteristic (ROC) curves]. After the program, participants completed a 7-point global perceived effect scale (GPE), based on which they were classified as "improved" vs. "stable." ROC curves computed the best cut-off level (taken as the MIC) between the two groups. ROC analysis was also performed on subgroups according to patients' baseline PCS scores. RESULTS: ES, SRM and MDC were 0.71, 0.67 and 7.73, respectively. ROC analysis yielded an MIC of 8 points (95% confidence interval [CI]: 6-10; area under the curve [AUC]: 0.88). ROC analysis of the PCS subgroups confirmed an MIC of 8 points (95%CI: 6-10) for no/low catastrophizers (score <30, N.=159; AUC: 0.90) and indicated an MIC of 11 points (95%CI: 8-14) for catastrophizers (score >30, N.=33; AUC: 0.84). CONCLUSIONS: The PCS-I showed good ability to detect patient-perceived clinical changes in chronic LBP postrehabilitation. The MIC values we determined provide a benchmark for assessing individual improvement in this clinical context. CLINICAL REHABILITATION IMPACT: The present study calculated - in a sample of people with chronic LBP - the responsiveness and MIC of the PCS. These values increase confidence in interpreting score changes, enhancing their meaningfulness for both research and clinical contexts.

Multimodal exercises integrated with cognitive-behavioural therapy improve disability of patients with failed back surgery syndrome: a randomized controlled trial with one-year follow-up.

PURPOSE: To evaluate the effect of multimodal exercises integrated with cognitive-behavioural therapy on disability, pain, and quality of life in patients suffering from failed back surgery syndrome (FBSS), and to appraise its extent in the long term. METHODS: By means of a parallel-group superiority-controlled trial, 150 outpatients were randomly assigned to a 10-week individual-based multimodal programme of task-oriented exercises integrated with cognitive-behavioural therapy (experimental group, 75 patients) or individual-based general physiotherapy (control group, 75 patients). Before treatment, 10 weeks later (post-treatment), and 12 months after the end of treatment, the Oswestry Disability Index (primary outcome), the Tampa Scale for Kinesiophobia, the Pain Catastrophising Scale, a pain intensity numerical rating scale and the Short-Form Health Survey were evaluated. Linear mixed model analysis for repeated measures was carried out for each outcome measure. RESULTS: Significant group (p < 0.001), time (p < 0.001), and time-by-group interaction (p < 0.001) effects were found for all outcome measures. Concerning disability, between-group differences (95% confidential interval) in favour of the experimental group of -9 (-10.7; -7.3) after training and of -13.2 (-14.7; -11.7) at follow-up were found. Also, kinesiophobia, catastrophising and pain showed significant between-group differences of 9, 12.5 and 1.7 points, respectively. CONCLUSION: The multimodal intervention proposed was superior to general physiotherapy in reducing disability, kinesiophobia, catastrophising, and enhancing the quality of life of patients with FBSS. The effects were reinforced one year after the programme ended.IMPLICATIONS FOR REHABILITATIONMultimodal exercises integrated with cognitive-behavioural therapy induced significant improvements in disability, pain, kinesiophobia, catastrophising, and quality of life of subjects with Failed Back Surgery Syndrome.A well-integrated rehabilitative team which contributes towards reaching intervention goals is advised.Physiotherapists should adopt task-oriented exercises to promote an earlier return to common activities of disabled patients.Psychologists should explain how to modify useless beliefs and support adequate behaviours, in order to produce constructive attitudes towards perceived disability.

Enrichment of Double RUNX1 Mutations in Acute Leukemias of Ambiguous Lineage.

Acute leukemia of ambiguous lineage (ALAL) is a rare type of leukemia and represents an unmet clinical need. In fact, due to heterogeneity, substantial rarity and absence of clinical trials, there are no therapeutic guidelines available. We investigated the genetic basis of 10 cases of ALAL diagnosed at our centre from 2008 and 2020, through a targeted myeloid and lymphoid sequencing approach. We show that this rare group of acute leukemias is enriched in myeloid-gene mutations. In particular we found that RUNX1 mutations, which have been found double mutated in 40% of patients and tend to involve both alleles, are associated with an undifferentiated phenotype and with lineage ambiguity. Furthermore, because this feature is typical of acute myeloid leukemia with minimal differentiation, we believe that our data strengthen the idea that acute leukemia with ambiguous lineage, especially those with an undifferentiated phenotype, might be genetically more closer to acute myeloid leukemia rather than acute lymphoblastic leukemia. These data enrich the knowledge on the genetic basis of ALAL and could have clinical implications as an acute myeloid leukemia (AML) - oriented chemotherapeutic approach might be more appropriate.

Multidisciplinary program based on early management of psychological factors reduces disability of patients with subacute low back pain: one-year results of a randomized controlled study.

BACKGROUND: Multidisciplinary rehabilitation induces disability improvement, pain reduction and favors return-to-work in patients with subacute low back pain (LBP). Current research advises additional high-quality trials. AIM: The aim of this study is to test the effect of a multidisciplinary rehabilitative program incorporating cognitive-behavioral interventions compared to general physiotherapy alone to treat subacute LBP, and to appraise its long-term extent. DESIGN: Randomised parallel-group superiority-controlled trial. SETTING: Outpatient rehabilitation hospital. POPULATION: One hundred and fifty patients with subacute LBP. METHODS: Patients were assigned randomly to a 10-week individual-based multimodal program of task-oriented exercises integrated with cognitive-behavioral therapy (experimental group, 75 patients) or individual-based general physiotherapy (control group, 75 patients). Before treatment, 10 weeks later (post-treatment), and 12 months after treatment, the staff administered the Oswestry Disability Index (ODI, primary outcome), a pain intensity numerical rating scale (NRS), the Tampa Scale for Kinesiophobia (TSK), the Pain Beliefs and Perception Inventory (PBAPI), the Hospital and Anxiety Depression Score (HADS) and the Coping Strategies Questionnaire-revised (CSQ-R). Linear mixed model analysis for repeated measures was carried out for each outcome measure. RESULTS: Significant group (P<0.001), time (P=0.002), and time-by-group interaction (P<0.001) effects were found for ODI, with a between-group difference (standard error) after training of 11.5 (1.0) and at follow-up of 15.7 (0.9), in favor of the experimental group. A significant interaction effect (P<0.001) was found for all secondary outcome measures, with significantly greater improvements in the experimental group, after rehabilitation and at follow-up. CONCLUSIONS: The multidisciplinary intervention was superior to general physiotherapy in reducing disability, pain, psychological factors and coping strategies of patients with subacute LBP. The effects were reinforced after one year. CLINICAL REHABILITATION IMPACT: Treatment of subacute LBP requires cognitive modifications closely linked to physical performances in order to achieve mental adjustments and guarantee cognitive-behavioral and motor lasting changes.

A further Rasch analysis of the Fear-Avoidance Beliefs Questionnaire in adults with chronic low back pain suggests the revision of its rating scale.

BACKGROUND: Low-back pain (LBP) is a common health problem and one of the leading causes of activity limitation and work absence. LBP determines high societal burdens, as it is the most common cause of medically certified sick leave and early retirement, with economic impacts similar to other high-cost conditions such as cancer, cardiovascular and autoimmune diseases. AIM: The aim of this study was to examine the psychometric properties of the Fear-Avoidance Beliefs Questionnaire (FABQ) and its two subscales, in subjects with chronic low back pain (LBP). DESIGN: Methodological research based on a cross-sectional observational study. SETTING: Outpatients consecutively admitted to our Rehabilitation Unit were enrolled between January and August 2015, before the beginning of an 8-week program of multidisciplinary rehabilitation. POPULATION: A convenience sample of 155 Italian subjects with chronic LBP (57% men; mean age: 43±11 years; mean pain duration: 23±32 months) completed the FABQ. METHODS: Rasch analysis was used to investigate dimensionality of the entire scale and key psychometric properties of its two subscales. RESULTS: The FABQ-Physical Activity (FABQ-PA) and FABQ-Work (FABQ-W) subscales showed two distinct unidimensional structures. Their 7-option rating categories were malfunctioning, but after collapsing problematic categories and omitting the central one ("unsure") the new 4 categories (completely disagree; disagree; agree; completely agree) functioned as intended. After that and accommodation of local response dependency between two items in a testlet solution, each of the two subscales presented acceptable fit to the Rasch model (just one FABQ-W items was slightly underfitting). Person separation reliability was acceptable, but not high (0.69 for FABQ-PA, and 0.79 for FABQ-W). CONCLUSIONS: FABQ-PA and FABQ-W have adequate unidimensionality. A simplification of the response options of both subscales is strongly recommended to improve the technical quality of the scale. The reliability indexes suggest FABQ-PA and FABQ-W can be used for group judgements about level of fear-avoidance beliefs, but not for clinical decision-making in individuals. The selection of their items is acceptable, although if future studies corroborate our results - there is room for some refinements to improve the general measurement quality. CLINICAL REHABILITATION IMPACT: Fear-avoidance beliefs are associated with reduction of physical activity, and development of disability and deconditioning. This study examined the measurement properties of the two FABQ subscales, showing their essential unidimensionality, recommending the simplification of the rating categories, and discussing strengths and weaknesses of item selection. Our results extend the evidence for FABQ as a satisfactory (but improvable) measure of fear-avoidance beliefs in chronic LBP.

Italian versions of the Urogenital Distress Inventory-6 and Incontinence Impact Questionnaire-7: translation and validation in women with urinary incontinence.

PURPOSE: To culturally adapt and validate the Urogenital Distress Inventory-6 and Incontinence Impact Questionnaire-7 (short forms) for use in Italian-speaking women with urinary incontinence. METHODS: We developed Italian versions of the two questionnaires through forward-backward translation, expert review and cognitive interviews. We then administered them to 100 women with urinary incontinence (mean age 58.02 ± 11.9 years) to assess the internal consistency (Cronbach's alpha), test-retest reliability (intraclass correlation coefficient), standard error of measurement, minimum detectable change, and construct validity by hypothesis testing. RESULTS: No difficulties in acceptability emerged. Internal consistency was 0.61 for Urogenital Distress Inventory-6 and 0.88 for Incontinence Impact Questionnaire-7. Test-retest reliability was respectively 0.79 and 0.91. The minimum detectable change was respectively 22.9 and 18.1 points (on a 0-100 scale). Nine out of 10 a priori hypotheses regarding construct validity were confirmed. CONCLUSIONS: The Italian versions of the Urogenital Distress Inventory-6 and Incontinence Impact Questionnaire-7 showed reliability levels in line with the literature and good construct validity. Thus, we think that the present study extends the evidence for both questionnaires as useful tools for assessing women with urinary incontinence.Implications for rehabilitationThe Italian versions of the short forms of the Urogenital Distress Inventory and the Incontinence Impact Questionnaire have never been validated in Italian-speaking women with urinary incontinence.After translation and cross-cultural adaptation, the Italian versions of these two questionnaires showed reliability levels in line with the literature and good construct validity.The Urogenital Distress Inventory-6 produces a summary index of overall symptom distress, whereas the Incontinence Impact Questionnaire-7 is a unidimensional questionnaire measuring the adverse effects of urinary incontinence on health-related quality of life.

Reliability, responsiveness and minimal clinically important difference of the two Fear Avoidance and Beliefs Questionnaire scales in Italian subjects with chronic low back pain undergoing multidisciplinary rehabilitation.

BACKGROUND: The Fear-Avoidance Beliefs Questionnaire (FABQ) is a widely used outcome measure. There is still a lack of information concerning responsiveness and minimal clinically important difference (MCID), limiting its use for clinical and research purposes. AIM: The aim of this study was to examine reliability, responsiveness and MCID of the two FABQ scales in subjects with chronic low back pain. DESIGN: Methodological research based on a prospective single-group observational study. SETTING: Outpatient, Unit of rehabilitation. POPULATION: Chronic non-specific low back pain. METHODS: At the beginning and the end of a multidisciplinary program (8-week), 129 subjects completed the FABQ scales. Reliability was determined as internal consistency (Cronbach's alpha) and test-retest reliability (96-hour interval; N.=64; Interclass correlation coefficient [ICC 2.1]). Responsiveness was calculated both by distribution-based and anchor-based methods, using as external criterion the Global Perceived Effect Scale (GPE: 7 levels), rated by each individual. RESULTS: Cronbach's alpha and ICC(2,1) were respectively: 0.75 and 0.90 for FABQ-Physical Activity Scale (FABQ-PA), and 0.85 and 0.95 for FABQ-Work Scale (FABQ-W). Minimum detectable change (MDC95) values were 3.69 points for FABQ-PA, and 5.95 points for FABQ-W. In receiver-operating characteristic curves, splitting GPE data into null/minimal/moderate improvement vs. large improvement (GPE 0-2 vs. GPE 3): 1) for FABQ-PA, the area under the curve (AUC) was 0.97 and the best cutoff score identifying meaningful change in fear-avoidance beliefs about physical activity was a change of 4 points; 2) for FABQ-W, the AUC was 0.97 and the best cutoff score for meaningful change in fear-avoidance beliefs about work activities was a change of 7 points. CONCLUSIONS: After triangulation of the above results, a change of 4 points for FABQ-PA and 7 points for FABQ-W were selected as MCID. These two values represent cutoffs that seem to accurately identify meaningful change in fear-avoidance beliefs, according to subject's judgement. CLINICAL REHABILITATION IMPACT: The present study calculated - in a sample of people with chronic low back pain - the minimal clinically important change of the two FABQ scales (FABQ-Physical Activity Scale and FABQ-Work Scale). These values increase confidence in interpreting score changes, thus enhancing their meaningful use in both research and clinical contexts.

The Italian version of the Quebec Back Pain Disability Scale: cross-cultural adaptation, reliability and validity in patients with chronic low back pain.

BACKGROUND AND AIM: Growing attention is being given to physical functioning measures to assess interventions for low back pain (LBP). The Quebec Back Pain Disability Questionnaire (QBPDS) has never been validated in Italian patients, and the aim of the study was culturally adapting and validating the Italian version of the QBPDS (QBPDS-I), to allow its use with Italian-speaking patients with chronic LBP. METHODS: The QBPDS-I was developed by means of forward-backward translation, a final review by an expert committee and a test of the prefinal version to evaluate its comprehensibility. The psychometric testing included structural validity by exploratory factor analysis (EFA), reliability by internal consistency (Cronbach's alpha) and test-retest reliability (intraclass correlation coefficient, ICC 2.1), measurement error by calculating the minimum detectable change (MDC), construct validity by assessing hypotheses of QBPDS correlations with the Roland Morris Disability Scale (RMDQ), the Oswestry Disability Questionnaire (ODI) and a pain numerical rating scale (NRS) (Spearman's correlations). RESULTS: It took one month to develop a consensus-based version of the QBPDS-I. The questionnaire was administered to 201 subjects with chronic LBP and was well accepted. EFA suggested a one-factor 20-item solution (first factor variance explained = 54.7%). Internal consistency (α = 0.95) and test-retest reliability (ICC = 0.90) were excellent. The MDC was 12 scale points. Construct validity was good as all of the hypotheses were met; correlations: RMDQ (r = 0.40), ODI (r = 0.48) and NRS (r = 0.44). CONCLUSIONS: The QBPDS-I is unidimensional, reliable and valid in patients with chronic LBP. Its use is recommended for clinical and research purposes.

Cross-cultural adaptation, reliability and validity of the Italian version of the craniofacial pain and disability inventory in patients with chronic temporomandibular joint disorders.

BACKGROUND: To develop an Italian version of the Craniofacial Pain Disability Inventory (CFPDI-I) and investigate its psychometric abilities in patients with temporomandibular disorders (TMD). METHODS: The CFPDI was translated following international standards. The psychometric analyses included reliability by internal consistency (Cronbach's alpha) and test/retest stability (intraclass correlation coefficient, ICC); construct validity was investigated by matching (a priori hypotheses) the CFPDI-I with the Italian Neck Disability Index (NDI-I), a pain intensity numerical rating scale (NRS), the Italian Pain Catastrophising Scale (PCS-I), the Italian Tampa Scale of Kinesiophobia (TSK-I), and the Italian Migraine Disability Assessment Score Questionnaire (MIDAS) (Pearson's correlation). Alpha was set at 0.05. RESULTS: Two hundred and twelve patients with chronic TMD completed the tool. The questionnaire was internally consistent (α = 0.95) and its stability was good (ICCs = 0.91). As hypothesised, validity figures showed CFPDI-I strongly correlated with the NDI-I (r = 0.66, p < 0.05) and moderately correlated with the NRS (r = 0.48, p < 0.05), PCS (r = 0.37, p < 0.05), TSKI (r = 0.35, p < 0.05) and MIDAS (r = 0.47, p < 0.05). Similar estimates were shown by CFPDI-I subscales. CONCLUSIONS: The cross-culturally adapted version of the Craniofacial Pain and Disability Inventory (CFPDI-I) showed satisfactory psychometric properties that replicate those of the original version and, therefore, can be implemented in the clinical assessment of Italian people affected by TMD.

Development of the Italian version of the trunk impairment scale in subjects with acute and chronic stroke. Cross-cultural adaptation, reliability, validity and responsiveness.

PURPOSE: To cross-culturally adapt and psychometrically analyse the Italian version of the Trunk Impairment Scale on acute (cohort 1) and chronic stroke patients (cohort 2). METHODS: The Trunk Impairment Scale was culturally adapted in accordance with international standards. The psychometric testing included: internal consistency (Cronbach's alpha), inter- and intra-rater reliability (intraclass correlation coefficient; standard error of measurement and minimal detectable change), construct validity by comparing Trunk Impairment Scale score with Barthel Index, motor subscale of Functional Independence Measure, and Trunk Control Test (Pearson's correlation), and responsiveness (Effect Size, Effect Size with Guyatt approach, standardized response mean, and Receiver Operating Characteristics curves). RESULTS: The Trunk Impairment Scale was administered to 125 and 116 acute and chronic stroke patients, respectively. Internal consistency was acceptable (α > 0.7), inter- and intra-rater reliability (ICC > 0.9, Minimal Detectable Change for total score < 1.6 in cohort 1 and < 1.1 in cohort 2) were excellent. The construct validity showed acceptable correlations (r > 0.4) with all scales but the motor Functional Independence Measure in cohort 2. Distribution-based methods showed large effects in cohort 1 and moderate to large effects in cohort 2. The Minimal Important Difference was 3.5 both from patient's and therapist's perspective in cohort 1 and 2.5 and 1.5 from patient's and therapist's perspective, respectively, in cohort 2. CONCLUSION: The Trunk Impairment Scale was successfully translated into Italian and proved to be reliable, valid, and responsive. Its use is recommended for clinical and research purposes. Implications for Rehabilitation Trunk control is an essential part of balance and postural control, constituting an important prerequisite for daily activities and function. The TIS administered in subjects with subacute and chronic stroke was reliable, valid and responsive. The TIS is expected to help clinicians and researchers by identifying key functional processes related to disability in people with subacute and chronic stroke.

Efficacy of two brief cognitive-behavioral rehabilitation programs for chronic neck pain: results of a randomized controlled pilot study.

BACKGROUND: Current models of pain behavior suggest that kinesiophobia prevents the reacquisition of normal function, promotes the development of maladaptive coping strategies, and contributes to the disability associated with chronic neck pain (NP). AIM: Comparing two brief cognitive-behavioral programs aimed at managing kinesiophobia to understand which one induces better short-term improvements in disability, fear of movement, catastrophizing, adaptive coping strategies, quality of life (QoL), and pain intensity of chronic NP. DESIGN: Pilot, randomized, controlled trial, 3-months follow-up. SETTING: Outpatients. POPULATION: Subjects with chronic NP. METHODS: The population was randomized into two groups: group A (N.=15) underwent four sessions of cognitive-behavioral therapy (CBT) based on the NeckPix© (1-week duration); group B (N.=15) received four sessions of CBT based on the Tampa Scale of Kinesiophobia (TSK) (1-week duration). Afterwards, both groups attended 10 sessions of multimodal exercises (5-week duration). Primary measure: Neck Disability Index (NDI). Secondary measures: NeckPix©, TSK, Pain Catastrophizing Scale, Chronic Pain Coping Inventory, EuroQol-Five Dimensions, and pain intensity Numerical Rating Scale. STATISTICS: Linear mixed model analyses for repeated measures for each outcome measure to evaluate changes over time and between group. RESULTS: A significant effect of time was found for all outcomes, while no outcomes showed group and/or interaction effects. No changes were found in terms of NDI at the end of CBT, while a significant improvement of about 13 points was found for both groups at the end of the motor training (P=0.001). Similarly, in terms of quality of life there was no change after the CBT program, and a significant change at the end of the motor training, with a partial loss at follow-up. From CBT sessions to follow-up both groups showed a progressive reduction in kinesiophobia, with each group achieving a bigger change in the specific scale used for the CBT program. CONCLUSIONS: Two brief cognitive-behavioral rehabilitation programs based on different methodologies of managing fear-avoidance beliefs induced similar short-term improvements in subjects with chronic NP. Clinically significant changes in terms of disability were found in both groups only at the end of a 5-week motor training, regardless of the cognitive-behavioral rehabilitation program previously administrated. CLINICAL REHABILITATION IMPACT: Treatment of chronic NP requires cognitive modifications closely linked to physical performances in order to achieve mental adjustments and guarantee cognitive-behavioral as well as motor lasting changes.

Molecular remission at the end of treatment is a necessary goal for a good outcome in ELN favorable-risk acute myeloid leukemia: a real-life analysis on 201 patients by the Rete Ematologica Lombarda network.

Favorable acute myeloid leukemia (AML) patients (pts.) demonstrate a relatively good outcome with standard induction; thus, pts. are generally not addressed to allogeneic transplant in first remission. However, it is not clear if also in a real-life setting, the outcome is homogeneous in the different favorable molecular groups and which are the parameters significantly associated to an increased relapse risk, useful to suggest the need of an intensified approach. In order to clarify this point, we collected clinical data on consecutive unselected AML pts. assigned to favorable category (modified ELN 2010 due to the inclusion of double-mutated CEBPA-positive cases), diagnosed and treated in six centers of the Italian network Rete Ematologica Lombarda (REL) from 2007 to 2015. We assessed response (CR, mCR), relapse rate (CIR), and outcome (OS, DFS) after first-line treatment. A total of 201 pts. was studied and the analysis was performed globally and in each molecular group: t(8;21)(q22;q22)/RUNX1-RUNX1T1 (30 pts., 14.9%), inv. (16)(p13q22) or t(16;16)(p13q22)/CBFB-MIH11 (35 pts., 17.4%), normal karyotype and mutated NPM1 and negative FLT3-ITD (116 pts., 57.7%) or double-mutated CEBPA (CEBPAdm) (20 pts., 10%). Complete remission (CR) was obtained in 188 pts. (93.5%), molecular CR (mCR) in 114 (67.5%); After a median follow-up of 2.4 years, cumulative incidence of relapse (CIR) was documented in 78 of 188 responding pts. (41%) after a median time of 11.3 months. CIR was higher in the CBFB-MIH11 group, in pts. achieving only a hematological response without mCR (72.1 vs 28.1%, p < 0.001), in older pts. and it resulted independently associated with a lower median cytarabine cumulative dose (CCD). Median OS was not reached: after 5 years it was 66.3%, and median DFS was 5.3 years, both without difference among groups. Molecular CR reached at any time, during or after the end of first-line treatment, was significantly associated with better DFS, and in particular, mCR assessed at the end of treatment was confirmed in multivariate analysis as an independent prognostic factor both for DFS and OS. In conclusion, the present study confirms in a real-life context the overall good prognosis of favorable-risk AML; the achievement of any molecular negativity during first-line treatment, particularly when assessed at the end of treatment, is associated with lower relapse and better survival. Increasing age at diagnosis has a negative prognostic impact, while CCD higher than 18 g/sqm is associated with better outcome.

Alternative splicing of hTERT: a further mechanism for the control of active hTERT in acute myeloid leukemia.

hTERT component is the key regulator of telomerase. Alternatively spliced variants of hTERT generate different telomerase activity. The goal of the study was to determine the role of different hTERT isoforms in the regulation of telomerase expression in AML patients. Among the 97 studied patients, 45 had a complex karyotype and 52 a normal karyotype. hTERT isoforms expression was determined in bone marrow samples by q-RT-PCR, using SYBR Green I. hTERT expression was lower in AML patients than controls (median 2.5 vs. 10.1, p = .003), though no difference was observed between the complex and normal karyotype (median 3.2 vs. 2.3, p = .37). High trans-dominant negative isoform expression increased the response rate by two. High expression of inactive product (-α - ß) was shown to increase the risk of relapse by about three times. In conclusion, our data suggest an intriguing link between the control of hTERT isoforms expression and AML outcome.

Responsiveness and minimal important change of the NeckPix© in subjects with chronic neck pain undergoing rehabilitation.

PURPOSE: The NeckPix© is a simple and rapid means of measuring the beliefs of subjects with chronic neck pain concerning pain-related fears of a specific set of activities of daily living. The original version showed satisfactory psychometric properties. This observational study is aimed at evaluating its responsiveness and minimal important changes (MICs) in subjects with chronic neck pain. METHODS: At the beginning, at the end of an 8-week rehabilitation programme as well as at the one-year follow-up, 153 subjects completed the NeckPix©. After the programme and at follow-up, subjects and physiotherapists also completed the global perceived effect (GPE) scale, which was divided to produce a dichotomous outcome. Responsiveness was calculated by distribution [effect size (ES); standardised response mean (SRM)] and anchor-based methods [receiver-operating characteristics (ROC) curves; correlations between change scores of the NeckPix© and GPEs]. ROC curves were also used to compute MICs. RESULTS: The ES ranged from 0.95 to 1.26 and the SRM from 0.84 to 0.98 at post-treatment and follow-up based on subjects' and physiotherapists' perspective. The ROC analyses revealed AUCs of 0.89 and 0.97 at post-treatment and follow-up, respectively; MICs (sensitivity; specificity) were of 6 (0.82; 0.88) and 8 (0.80; 0.92) at post-treatment and of 8 (0.95; 0.90 based on subjects and 0.95; 0.92 based on physiotherapists perspective) at follow-up. The correlations between change scores of the NeckPix© and GPEs ranged from -0.69 to -0.82. CONCLUSIONS: The NeckPix© was sensitive in detecting clinical changes in subjects with chronic neck pain undergoing rehabilitation. We recommend taking the MICs provided into account when assessing subjects' improvement or planning studies in this clinical context.

Responsiveness and Minimal Important Changes of the Scoliosis Research Society-22 Patient Questionnaire in Subjects With Mild Adolescent and Moderate Adult Idiopathic Scoliosis Undergoing Multidisciplinary Rehabilitation.

STUDY DESIGN: Single-center, prospective study. OBJECTIVE: Evaluating the responsiveness and minimal important changes (MICs) for the Scoliosis Research Society-22 Patient Questionnaire (SRS-22) in adolescent idiopathic scoliosis (AIS) and adult idiopathic scoliosis (AS). SUMMARY OF BACKGROUND DATA: Despite the SRS-22 properties have been investigated in various different languages, there is still a lack of information concerning responsiveness and MIC, limiting the use of SRS-22 for clinical and research purposes. METHODS: At the beginning and end of multidisciplinary rehabilitation programs, 149 subjects with mild AIS (Cobb angle <25°) and 140 subjects with moderate AS (Cobb angle <35°) completed the SRS-22. Upon completing the programs, subjects also performed the global perceived effect (GPE) scales test, which was divided to produce a dichotomous outcome (improved vs. stable). Responsiveness was calculated for all SRS-22 domains but satisfaction with management by distribution (effect size; standardized response mean) and anchor-based methods (receiver operating characteristic [ROC] curves; correlations between change scores of the SRS-22 and GPE). ROC curves were also used to compute the MICs. RESULTS: The effect size ranged from 1.23 to 1.50 in AIS and from 1.02 to 1.37 in AS. The standardized response mean ranged from 0.95 to 1.27 in AIS and from 0.66 to 0.90 in AS. The ROC analyses revealed the following MIC values (area under the curve; sensitivity; specificity): function, 0.70 (0.739;66;70) for AIS and 0.60 (0.842;84;76) for AS; pain, 0.70 (0.731;71;70) for AIS and 0.40 (0.817;81;70) for AS; mental health, 0.50 (0.708;83;58) for AIS and 0.55 (0.750;69;78) for AS; self-perceived image, 0.40 (0.609;79;42) for AIS and 0.60 (0.751;61;82) for AS. Correlations between change scores of the SRS-22 domains and GPE were low to moderate, ranging from -0.347 to -0.667. CONCLUSION: The SRS-22 was sensitive in detecting clinical changes in subjects with adolescent and adult scoliosis. We recommend taking the MICs provided into account when assessing patients' improvement or planning studies in these clinical contexts. LEVEL OF EVIDENCE: 3.

MDS/AML del(11)(q14) Share Common Morphological Features Despite Different Chromosomal Breakpoints.

In myelodysplatic syndromes and acute myeloid leukemia (MDS/AML) deletion of the 11q14 region is a rare chromosomal defect (incidence: 0.6-1.0%), included within the intermediate risk criteria by the International Prognostic Scoring System. No fluorescence in situ hybridization (FISH) study has yet been performed to identify a common breakpoint region (CBR). In our study through FISH with bacterial artificial chromosomes and commercial probes, we analyzed seven patients with MDS/AML harboring 11q14 deletion on conventional cytogenetic analysis. FISH revealed deletions in five patients and amplifications in two. Three patients with deletion carried a CBR, two had a deletion involving a more centromeric breakpoint. These five patients exhibited multilineage dysplasia, blast cells with large round nuclei, loose chromatin, small and abundant nucleoli, and vacuolated cytoplasm with very thin Auer bodies. In conclusion, the morphological features which occur independently of the extent of the deletion are of multilineage dysplasia in MDS and leukemic blasts strongly reactive to peroxidase in AML; despite the variable size of the deleted area, some patients harbor a CBR.

'Real-life' study of imatinib therapy in chronic phase-chronic myeloid leukemia: A novel retrospective observational longitudinal analysis.

OBJECTIVES: Imatinib is a cornerstone of treatment of chronic myeloid leukemia. It remains unclear whether transient treatment discontinuation or dose changes affect outcome and this approach has not yet been approved for use outside clinical trials. METHODS: We conducted a retrospective single-institution observational study to evaluate factors affecting response in 'real-life' clinical practice in 138 chronic myeloid leukemia patients in chronic phase treated with imatinib. We used a novel longitudinal data analytical model, with a generalized estimating equation model, to study BCR-ABL variation according to continuous standard dose, change in dose or discontinuation; BCR-ABL transcript levels were recorded. Treatment history was subdivided into time periods for which treatment was given at constant dosage (total 483 time periods). Molecular and cytogenetic complete response was observed after 154 (32%) and 358 (74%) time periods, respectively. RESULTS: After adjusting for length of time period, no association between dose and cytogenetic complete response rate was observed. There was a significantly lower molecular complete response rate after time periods at a high imatinib dosage. DISCUSSION: This statistical approach can identify individual patient variation in longitudinal data collected over time and suggests that changes in dose or discontinuation of therapy could be considered in patients with appropriate biological characteristics.