New York Heart Association class and pulmonary artery pressure as prognostic factors of interstitial lung disease survival.

OBJECTIVE: The aim of this study was to evaluate New York Heart Association (NYHA) class and systolic pulmonary artery pressure (sPAP) as survival predictors in major interstitial lung diseases (ILD) including idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP) and hypersensitivity pneumonitis (HP) and in other ILD like granulomatosis with polyangiitis (GPA). PATIENTS AND METHODS: We analyzed survival, NYHA class, sPAP, and Octreoscan uptake index (UI) in 104 ILD patients (59 IPF, 19 NSIP, 10 HP and 16 GPA; median age 60.5 years) all referred to a single centre. RESULTS: Median survival was 68 months, with 1- and 2-year survival of 91% and 78%, respectively. Survival was lower among IPF and NSIP vs. HP and GPA patients (p=0.01). NYHA class 3-4 was more frequent among IPF (76.3%) vs. NSIP patients (31.6%; p<0.001). HP and GPA had NYHA class 1-2. NYHA class was negatively associated with survival (class 1=90.3 months vs. class 3=18.3 months and class 4=5.1 months; p=0.001). sPAP was >55 mmHg in 76.3% of patients with IPF and 35-55 mmHg in 63.2% of patients with NSIP. Patients with HP and GPA had sPAP < 55 mmHg. Among patients with IPF, NYHA and sPAP were negatively associated with survival (p<0.01) both showed a parallel trend. High-resolution computed tomography and survival were worse among IPF and NSIP vs. HP and GPA patients (p<0.001). Octreoscan UI was <10, 10-12, and >12 in IPF, NSIP, HP and GPA, respectively. Octreoscan UI was negatively associated with survival (p=0.002). CONCLUSIONS: NYHA class and sPAP are comparable ILD survival predictors. NYHA class is correlated with worse prognosis for IPF and NSIP vs. HP and GPA patients.

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.

Stem cells therapy in acute myocardial infarction: a new era?

Stem cells transplantation after acute myocardial infarction (AMI) has been claimed to restore cardiac function. However, this therapy is still restricted to experimental studies and clinical trials. Early un-blinded studies suggested a benefit from stem cell therapy following AMI. More recent blinded randomized trials have produced mixed results and, notably, the last largest pan-European clinical trial showed the inconclusive results. Furthermore, mechanisms of potential benefit remain uncertain. This review analytically evaluates 34 blinded and un-blinded clinical trials comprising 3142 patients and is aimed to: (1) identify the pros and cons of stem cell therapy up to a 6-month follow-up after AMI comparing benefit or no effectiveness reported in clinical trials; (2) provide useful information for planning future clinical programs of cardiac stem cell therapy.

Single-nucleotide polymorphisms in 3'-untranslated region inducible costimulator gene and the important roles of miRNA in alopecia areata.

Background: Alopecia areata (AA) spares the stem cell compartment and attacks only the base of the hair follicle, which is surrounded by infiltrating lymphocytes. AA is associated with polymorphisms in immune-related genes and with decreased function of CD4+CD25+ T regulatory (Treg) cells. Treg function is modulated by the costimulatory molecules, like inducible costimulator (ICOS) that are crucial in orienting T cell differentiation and function so that they strongly impact on the immunologic decision between tolerance or autoimmunity development. Objective: The aim of our study was to investigate the possible association of AA with single-nucleotide polymorphisms (SNP) present in the ICOS 3'-untranslated region (3'UTR) region and to elucidate how SNPs modulate ICOS gene expression by affecting miRNA binding sites. Methods: This is a case-control study performed in 184 patients with AA and 200 controls. ICOS gene and miRNA expression were analyzed by real-time polymerase chain reaction. Results: The genotype carrying the rs4404254(C) [p = 0.012, OR (95% CI): 0.5 (0.3-0.8)] and rs4675379(C) [p = 0.015, OR (95% CI): 0.3 (0.1-0.8)] 3' UTR alleles was more frequently observed in AA patients than in controls and correlated with a reduced ICOS expression. miR-1276 significantly suppressed ICOS expression by binding to the 3'UTR of ICOS mRNA. Also, we observed that, miR-101 and miR-27b are upregulated, while miR-103 and miR-2355-3p are downregulated in peripheral blood mononuclear cells of AA patients compared to controls. Conclusion: Our data show that rs4404254 and rs4675379 SNPs of ICOS gene are associated with AA and also reveal that the presence of rs4404254 polymorphism correlates with ICOS post-transcriptional repression by microRNA binding.

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.

Intraconal orbital displacement of a dental implant treated with an endoscopically-assisted approach.

Foreign bodies in the orbit are uncommon, and dental intraconal displacement is even more rare. We aim to present and discuss what is to our knowledge the first case and its management. A 55-year-old woman had a dental implant placed in the upper right maxilla, but during the procedure it was displaced into the orbit. It was removed reliably and safely through an enlarged endoscopic medial maxillectomy.

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.

Evaluation of membrane-bound and soluble forms of human leucocyte antigen-G in systemic sclerosis.

Systemic sclerosis (SSc) is a complex disease characterized by immune dysregulation, extensive vascular damage and widespread fibrosis. Human leucocyte antigen-G (HLA-G) is a non-classic class I major histocompatibility complex (MHC) molecule characterized by complex immunomodulating properties. HLA-G is expressed on the membrane of different cell lineages in both physiological and pathological conditions. HLA-G is also detectable in soluble form (sHLA-G) deriving from the shedding of surface isoforms (sHLA-G1) or the secretion of soluble isoforms (HLA-G5). Several immunosuppressive functions have been attributed to both membrane-bound and soluble HLA-G molecules. The plasma levels of sHLA-G were higher in SSc patients (444·27 ± 304·84 U/ml) compared to controls (16·74 ± 20·58 U/ml) (P < 0·0001). The plasma levels of transforming growth factor (TGF)-ß were higher in SSc patients (18 937 ± 15 217 pg/ml) compared to controls (11 099 ± 6081 pg/ml; P = 0·003), and a significant correlation was found between TGF-ß and the plasma levels of total sHLA-G (r = 0·65; P < 0·01), sHLA-G1 (r = 0·60; P = 0·003) and HLA-G5 (r = 0·47; P = 0·02). The percentage of HLA-G-positive monocytes (0·98 ± 1·72), CD4+ (0·37 ± 0·68), CD8+ (2·05 ± 3·74) and CD4+ CD8+ double-positive cells (14·53 ± 16·88) was higher in SSc patients than in controls (0·11 ± 0·08, 0·01 ± 0·01, 0·01 ± 0·01 and 0·39 ± 0·40, respectively) (P < 0·0001). These data indicate that in SSc the secretion and/or shedding of soluble HLA-G molecules and the membrane expression of HLA-G by peripheral blood mononuclear cells (PBMC) is clearly elevated, suggesting an involvement of HLA-G molecules in the immune dysregulation of SSc.

From art to science: the functional damage due to thumb osteoarthritis finely described by Velazquez 300 years before its clinical description.

Velazquez showed to know the entity of thumb osteoarthritis by finely describing it in one of his paintings. The concepts of anatomical damage, loss of strenght, and functional impairment are transmitted to the observer.

The pedicled buccal fat pad in oral reconstruction.

AIM: Aim of the study was to present a follow-up on 46 cases in which pedical buccal fat pad (BFP) flaps were used to repair oral defects without any additional local flaps or skin grafts. METHODS: The study comprised 46 patients, 31 men and 15 women, with an age range of 30-78 years (mean age 57.3 years). They were treated with a pedicled flap to repair defects of the ipsilateral maxilla (anterior or posterior), soft palate or retromolar mandibular area following tumor resection, osteonecrosis or the closure of oro-antral fistulae. The defects ranged from 2 × 2.5 cm to 4.5 × 5 cm. All patients were treated under general anesthesia. RESULTS: The flap fully covered the intraoral defect with any aesthetic deficits. After one month, the flap was fully epithelialized and of adequate thickness in all cases. Three postoperative complications were reported: one superficial necrosis and two small fistulae. CONCLUSION: Although the BFP has long been recognized and despite the simplicity of preparing the flap itself, numerically significant reports concerning the use of this technique in reconstructive facial surgery have only recently been published. The pedicled buccal fat flap is convenient and reliably repairs oral defects up to 4.5 cm in diameter on the ipsilateral side of the soft and hard palate, posterior alveolar region of the maxilla and the retromolar mandibular area. The surgical procedure is simple and morbidity at the donor site in not significant.

Contributing to the growth of Physical and Rehabilitation Medicine (PRM): call for a Cochrane Field in PRM.

The European Society of Physical and Rehabilitation Medicine (ESPRM), together with the European Journal of PRM and the PRM Section and Board of the European Union of Medical Specialists (UEMS), started an action to establish a relationship with Cochrane (formerly the Cochrane Collaboration). Cochrane is a global, independent network of researchers, professionals, patients, carers and people interested in health, with contributors from more than 130 countries. Its aim is to produce credible, accessible health information that is free from any conflicts of interest. Cochrane produces the Cochrane Library, an evidence-based resource that includes today more than 6300 Cochrane systematic reviews. Cochrane is made up of many different review groups and other entities (such as Centres and Branches), distributed around the world, that are mainly focused on specific healthcare problems (diseases, or organs). Inside Cochrane also Fields have been created, that focus on a dimension of health care other than a specific healthcare problem. A Cochrane Field represents a bridge between Cochrane and the stakeholders of the related healthcare area. The medical specialty of PRM is covering a broad medical domain: it deals with function, activities and participation in a large number of health conditions, mostly but not exclusively musculoskeletal, neurological and cardiorespiratory. Consequently, the currently more than 200 existing Cochrane Reviews are scattered among different groups. A PRM Field could greatly serve to the need of the specialty, spreading the actual Cochrane knowledge, focusing needs today not covered by Cochrane Reviews, facing the intrinsic methodological problems of the specialty. This paper introduces a call for the development of a PRM Cochrane Field, briefly reviewing what Cochrane is and how it is organized, defining the value and identifying a pathway toward the development of a PRM Cochrane Field, and finally shortly reviewing the Cochrane reviews of PRM interest.

Pain in stroke patients: characteristics and impact on the rehabilitation treatment. A multicenter cross-sectional study.

BACKGROUND: Post-stroke pain (PSP) is a common and disabling complication, difficult to treat, that often decreases patients' quality of life (QoL). The hypothesis is that PSP may negatively affect rehabilitation treatment. AIM: The aim of this paper was to quantify and characterize pain in a sample of post-stroke patients undergoing rehabilitation and to investigate the impact of pain in slowing down or discontinuing the rehabilitation program. DESIGN: Multicenter cross-sectional study. SETTING: Inpatients and outpatients of rehabilitation department. POPULATION: One hundred and six subacute and chronic stroke patients. METHODS: Pain intensity was measured with the NRS or the PAINAD (if cognitive/language impairment was present); pain characteristics were assessed with the DN4, and NPSI questionnaire. Qol was measured with the SF-36. A clinical assessment and a semi-structured questionnaire on pain occurrence, impact, and management was administered by the physiotherapist in charge of the patients and by the physician. RESULTS: Nearly 1/3 of the patients (32.9%) with normal cognitive functions and language reported pain occurrence after stroke; 81.8% of them had NRS≥3 and 31.8% DN4≥4 (meaning neuropathic origin of pain). In about 20% of the patients the PAINAD was used to measure pain; 17.4% of them presented a score ≥3. In 24.5% of our sample, pain influenced rehabilitation treatment. In 16% of the whole sample, pain influenced patients' attention during rehabilitation session. Patients with hypoesthesia presented significantly higher neuropathic pain scores than patients with normal sensory function. Regarding QoL, we found that patients with higher neuropathic pain showed more severe deterioration of mental aspects of QoL, where patients with higher nociceptive pain presented more severe deterioration of physical aspects of QoL. CONCLUSION: The results from this multicenter study showed that in about » of the patients, pain negatively influenced the rehabilitation program delaying the recovery and likely increasing the cost of rehabilitation. CLINICAL REHABILITATION IMPACT: Clinicians should pay more attention to pain, especially neuropathic pain, in post-stroke patients. Tailored pharmacological therapy, to treat and prevent pain, might improve patients' compliance during the rehabilitation process.