How well can the clinician appraise the patient's perception of the severity and impact of their back problem?

PURPOSE: A main concern of patients with back problems is pain and its impact on function and quality of life. These are subjective phenomena, and should be probed during the clinical consultation so that the physician can ascertain the extent of the problem. This study evaluated the agreement between clinicians' and patients' independent ratings of patient status on the Core Outcome Measures Index (COMI). METHODS: This was an analysis of the data from 5 spine specialists and 108 patients, in two centres. Prior to the consultation, the patient completed the COMI. After the consultation, the clinician (blind to the patient's version) also completed a COMI. Concordance was assessed by % agreement, Kappa values, Bland-Altman plots, Spearman rank, Intraclass Correlation Coefficients and comparisons of mean values, as appropriate. RESULTS: Agreement regarding the "main problem" (back pain, leg/buttock pain, sensory disturbances, other) was 83%, Kappa = 0.70 (95%CI 0.58-0.81). Moderate/strong correlations were found between the doctors' and patients' COMI-item ratings (0.48-0.74; p < 0.0001), although compared with the patients' ratings the doctors systematically underestimated absolute values for leg pain (p = 0.002) and dissatisfaction with symptom state (p = 0.002), and overestimated how much the patient's function was impaired (p = 0.029). CONCLUSION: The doctors were able to ascertain the location of the main problem and the multidimensional outcome score with good accuracy, but some individual domains were systematically underestimated (pain, symptom-specific well-being) or overestimated (impairment of function). More detailed/direct questioning on these domains during the consultation might deliver a better appreciation of the impact of the back problem on the patient's daily life.

MicroRNA-based signatures impacting clinical course and biology of ovarian cancer: a miRNOmics study.

BACKGROUND: In Western countries, ovarian cancer (OC) still represents the leading cause of gynecological cancer-related deaths, despite the remarkable gains in therapeutical options. Novel biomarkers of early diagnosis, prognosis definition and prediction of treatment outcomes are of pivotal importance. Prior studies have shown the potentials of micro-ribonucleic acids (miRNAs) as biomarkers for OC and other cancers. METHODS: We focused on the prognostic and/or predictive potential of miRNAs in OC by conducting a comprehensive array profiling of miRNA expression levels in ovarian tissue samples from 17 non-neoplastic controls, and 60 tumor samples from OC patients treated at the Regina Elena National Cancer Institute (IRE). A set of 54 miRNAs with differential expression in tumor versus normal samples (T/N-deregulated) was identified in the IRE cohort and validated against data from the Cancer Genoma Atlas (TCGA) related to 563 OC patients and 8 non-neoplastic controls. The prognostic/predictive role of the selected 54 biomarkers was tested in reference to survival endpoints and platinum resistance (P-res). RESULTS: In the IRE cohort, downregulation of the 2 miRNA-signature including miR-99a-5p and miR-320a held a negative prognostic relevance, while upregulation of miR-224-5p was predictive of less favorable event free survival (EFS) and P-res. Data from the TCGA showed that downregulation of 5 miRNAs, i.e., miR-150, miR-30d, miR-342, miR-424, and miR-502, was associated with more favorable EFS and overall survival outcomes, while miR-200a upregulation was predictive of P-res. The 9 miRNAs globally identified were all included into a single biologic signature, which was tested in enrichment analysis using predicted/validated miRNA target genes, followed by network representation of the miRNA-mRNA interactions. CONCLUSIONS: Specific dysregulated microRNA sets in tumor tissue showed predictive/prognostic value in OC, and resulted in a promising biological signature for this disease.

Efficacy of bracing in early infantile scoliosis: a 5-year prospective cohort shows that idiopathic respond better than secondary-2021 SOSORT award winner.

PURPOSE: In conservative early onset scoliosis treatment, interest in bracing is growing because repeated general anaesthesia (required by casting) has been questioned for possible brain damages. We aimed to check the results in the medium term of bracing, comparing idiopathic (IIS) to secondary (SIS) infantile scoliosis. METHODS: We performed a retrospective study in a consecutive prospective cohort. Inclusion criteria were: discovery of scoliosis and bracing below age 3; exclusion criteria: previous spine surgery, less than three consultations. We considered the following results: full (< 20° Cobb) and partial (< 30°) success; hold-up (progression < 5° but curve > 29°); partial (progression > 5°) and full (fusion) failure; statistics: ANOVA for repeated measures; linear mixed effect model with Cobb angle (dependent), time and diagnosis (independent) variables. RESULTS: We included 34 infants (16 IIS and 18 SIS) of age 1·10 ± 0·10 (years·months), 44 ± 17° curves, 27 ± 10° rib vertebral angle difference, average observation 5·05 ± 3·03 years. We found progressive improvement of IIS and stability of SIS patients. Six IIS (37.5%) and one SIS (6%) reached brace weaning before puberty with 13 ± 5° (improvement 61 ± 15%, p < 0.001), after 4·11 ± 3·07 years of treatment. Three patients were fused, one IIS (6%) and two SIS (11%). Two IIS patients also reached end-of-growth with 18° (start 40° at 1·03 years) and 20° (start 32° at 2·12 years), respectively. CONCLUSION: Bracing shows promising results in the medium term for high-degree IIS, with very few hold-ups (19%) and failures (12%). Conversely, failures prevail for SIS (full 11%), even if the partial failure (39%) is still a time-buying strategy.

Bracing adults with chronic low back pain secondary to severe scoliosis: six months results of a prospective pilot study.

PURPOSE: Adult scoliosis is sometimes associated with back pain and severe curves can progress over time. Despite scoliosis has been estimated to affect up to 68% of the population over 60, there is scant literature about conservative treatment for adult scoliosis. Recently, we tested a new brace designed to alleviate pain for adult patients with chronic pain secondary to scoliosis. The study aims to test the efficacy of a prefabricated brace in reducing pain in adult scoliosis patients. METHODS: Twenty adults (age 67.8 ± 10.5, curve 61.9 ± 12.6° Cobb) with chronic low back pain (cLBP) secondary to Idiopathic Scoliosis (IS) were included. Patients were evaluated at baseline immediately before starting with the brace and after 6 months. Outcome measures were GRS, Oswestry Disability Index (ODI), Roland Morris Questionnaire (RM), COMI. The paired t test, ANOVA and Wilcoxon tests were used for statistical analysis RESULTS: At six months, worst pain, leg pain and back pain were significantly improved: from 7.15 to 5.60, from 5.65 to 4.35 and from 6.55 to 5.25 (p < 0.05). Sixty-five percent of patients achieved the minimal clinically important difference of 2 points for worst pain and leg pain, 55% for back pain. RM and COMI improved (p < 0.05), no differences for ODI. CONCLUSION: The prefabricated brace showed a significant improvement at 6 months of worst, leg and back pain in most patients in a group of adult women with IS and cLBP. The quality of life didn't change in a clinically significant way even if the patients reported satisfaction with the treatment. Trial registration number and date of registration: ClinicalTrials.gov Identifier: NCT02643290, December 31, 2015.

Reliability, repeatability and comparison to normal of a set of new stereophotogrammetric parameters to detect trunk asymmetries.

Aesthetic impairment is a crucial issue in Adolescent Idiopathic Scoliosis (AIS), but to date no objective measurements are available. The aim of the study is to evaluate the repeatability of 17 parameters measured by surface topography in a group of AIS subjects and verify their diagnostic validity. The paper is divided into three cross-sectional observational studies. We evaluated 17 selected surface topography parameters that could be good predictors of scoliosis' impact on the patients' trunk. We analysed short-term (30 seconds, 38 subjects) and medium-term (90 minutes, 14 subjects) repeatability of surface topography measures and their diagnostic validity in AIS (74 subjects, 33 AIS patients and 41 healthy subjects). All examined parameters were highly correlated as far as short and medium-term repeatability is concerned. We found a statistically significant difference between the scoliosis group and the control group in 3 surface rotation parameters, 1 shoulder parameter and 3 waist parameters. In conclusion, surface topography showed a good repeatability. Moreover, some of its parameters are correlated with AIS, enabling us to find differences between pathological and healthy subjects. Thanks to these findings, it will be possible to develop a tool that can objectively evaluate aesthetics is AIS patients.

Correction to: The "Risser+" grade: a new grading system to classify skeletal maturity in idiopathic scoliosis.

Unfortunately, the affiliation of the author Negrini S has been incorrectly published in the original version. The complete correct affiliation of this author should read as follows.

The "Risser+" grade: a new grading system to classify skeletal maturity in idiopathic scoliosis.

PURPOSE: This study aims to propose and validate a new unified "Risser+" grade that combines the North American (NA) and European (EU) variants of the classic Risser score. The "Risser+ " grade can effectively combine the North American and European Risser Classifications for skeletal maturity with adequate intra-rater/inter-rater reliability and agreement. METHODS: Agreement and reliability were evaluated for 6 raters (3-NA, 3-EU) who assessed 120 pelvic radiographs from the BrAIST trial, all female, average age 13.4 (range 10.1-16.5 years). Blinded raters reviewed x-rays at two time-points. Intra- and inter-rater agreement (RA) were established with Krippendorff's alpha (k-alpha), while intra- and inter-rater reliability (RR) were established with intraclass correlation coefficients (ICC). Acceptable agreement and reliability were set a priori at 0.80. RESULTS: Inter-RA for the second reading met study requirements (k-alpha = 0.86 [0.81-0.90]) compared to the first reading (0.72 [0.63-0.79]) while combined readings was close to target agreement (0.79 [0.74-0.84]). Removal of 20 readings demonstrating outlier tendencies increased agreement for the first, second, and combined reads (k-alpha = 0.85, 0.89, 0.87, respectively). Intra-RA was sufficient for 4 out of 6 raters (k-alpha > 0.80) and one rater from EU and NA presented subpar intra-RA (k-alpha = 0.64 and 0.74, respectively). Inter-RR met study requirements overall reads (ICC = 0.96 [0.95-0.97]) including the first (0.94 [0.92-0.95]) and second (0.97 [0.97-0.98]) reads, independently. CONCLUSIONS: The Risser+ system showed excellent reliability across multiple reads and raters and demonstrated 79% agreement overall reads and ratings. Agreement increased to over 85% when raters could distinguish Risser 0 + from Risser 5. These slides can be retrieved from electronic supplementary material.

Gain-of-function mutant p53 downregulates miR-223 contributing to chemoresistance of cultured tumor cells.

Mutant p53 proteins are expressed at high frequency in human tumors and are associated with poor clinical prognosis and resistance to chemotherapeutic treatments. Here we show that mutant p53 proteins downregulate micro-RNA (miR)-223 expression in breast and colon cancer cell lines. Mutant p53 binds the miR-223 promoter and reduces its transcriptional activity. This requires the transcriptional repressor ZEB-1. We found that miR-223 exogenous expression sensitizes breast and colon cancer cell lines expressing mutant p53 to treatment with DNA-damaging drugs. Among the putative miR-223 targets, we focused on stathmin-1 (STMN-1), an oncoprotein known to confer resistance to chemotherapeutic drugs associated with poor clinical prognosis. Mutant p53 silencing or miR-223 exogenous expression lowers the levels of STMN-1 and knockdown of STMN-1 by small interfering RNA increases cell death of mutant p53-expressing cell lines. On the basis of these findings, we propose that one of the pathways affected by mutant p53 to increase cellular resistance to chemotherapeutic agents involves miR-223 downregulation and the consequent upregulation of STMN-1.

MicroRNA-128-2 targets the transcriptional repressor E2F5 enhancing mutant p53 gain of function.

p53 mutations have profound effects on non-small-cell lung cancer (NSCLC) resistance to chemotherapeutic treatments. Mutant p53 proteins are usually expressed at high levels in tumors, where they exert oncogenic functions. Here we show that p53R175H, a hotspot p53 mutant, induces microRNA (miRNA)-128-2 expression. Mutant p53 binds to the putative promoter of miR128-2 host gene, ARPP21, determining a concomitant induction of ARPP21 mRNA and miR-128-2. miR-128-2 expression in lung cancer cells inhibits apoptosis and confers increased resistance to cisplatin, doxorubicin and 5-fluorouracyl treatments. At the molecular level, miR-128-2 post-transcriptionally targets E2F5 and leads to the abrogation of its repressive activity on p21(waf1) transcription. p21(waf1) protein localizes to the cytoplasmic compartment, where it exerts an anti-apoptotic effect by preventing pro-caspase-3 cleavage. This study emphasizes miRNA-128-2 role as a master regulator in NSCLC chemoresistance.

Two different techniques in the rehabilitation treatment of low back pain: a randomized controlled trial.

AIM: The Back School is a widely accepted and effective method for treating low back pain, whereas no scientific evidence exists about the effects of the Pilates CovaTech method. With this study we wanted to evaluate the efficacy of this new method in patients with low back pain. METHODS: Fifty-three patients with at least 3 months of nonspecific low back pain were entered into a Pilates therapy or a Back School treatment group, 43 of which completed the study. Small exercise groups of 7 patients each followed a daily kinesitherapy protocol for 10 days. Evaluations were performed at the start of the study and then at 1, 3 and 6 months after the beginning of treatment. We used the Oswestry Low Back Pain Disability Scale (OLBPDQ) to assess disability and the visual analog scale (VAS) to evaluate pain. RESULTS: Demographic and baseline clinical characteristics were similar for both groups. A significant reduction in pain intensity and disability was observed across the entire sample. The Pilates method group showed better compliance and subjective response to treatment. CONCLUSIONS: The results obtained with the Pilates method were comparable to those achieved with the Back School method, suggesting its use as an alternative approach to the treatment of non specific low back pain.