FLT3-targeted therapy restores GATA1 pathway function in NPM1/FLT3-ITD mutated acute myeloid leukaemia.

One-third of newly diagnosed adult acute myeloid leukaemia (AML) carry FLT3 mutations, which frequently occur together with nucleophosmin (NPM1) mutations and are associated with worse prognosis. FLT3 inhibitors are widely used in clinics with limitations due to drug resistance. AML cells carrying FLT3 mutations in both mouse models and patients present low expression of GATA1, a gene involved in haematopoietic changes preceding AML. Here, we show that FLT3 inhibition induces cellular responses and restores the GATA1 pathway and functions in NPM1/FLT3-ITD mutated AML, thus providing a new mechanism of action for this drug.

One-shot platelet-rich plasma (PRP) injection is non-inferior to extracorporeal shockwave therapy in the management of supraspinatus tendinosis.

PURPOSE: Supraspinatus tendinosis (ST) refers to the intratendinous degeneration of the supraspinatus tendon. Platelet-Rich Plasma (PRP) is one of the possible conservative treatments for supraspinatus tendinosis. This prospective observational study aims to evaluate the efficacy and safety of a single ultrasound-guided PRP injection in the treatment of supraspinatus tendinosis and to assess its non-inferiority to the widely used shockwave therapy. METHODS: Seventy-two amateur athletes (35 male, mean age: 43.75 ± 10.82, range 21-58 years old) with ST were finally included in the study. All the patients underwent clinical evaluation at baseline, (T0) and at 1-month (T1), 3-month (T2) and 6-month (T3) follow-up using the following clinical scales: the Visual Analogue Scale for pain (VAS), Constant Score and the Disabilities of the Arm, Shoulder and Hand Score (DASH). A T0 and T3 ultrasound examination was also performed. The findings observed in the recruited patients were compared to the clinical results observed in a retrospective control group made up of 70 patients (32 male, mean age = 41.29 ± 13.85, range 20-65 years old) treated by extracorporeal shockwave therapy (ESWT). RESULTS: VAS, DASH and Constant scores significantly improved from T0 to T1; the improvement in clinical scores was kept until T3. No local nor systemic adverse events were observed. An improvement in the tendon structure was observed on ultrasound examination. PRP showed a non-statistical inferiority, in terms of efficacy and safety, compared to ESWT. CONCLUSION: The PRP one-shot injection is a valid conservative treatment to reduce pain, and improve both quality of life and functional scores in patients with supraspinatus tendinosis. Furthermore, the PRP intratendinous one-shot injection showed a non-inferiority in terms of efficacy at the 6-month follow-up, compared to ESWT.

Total Worker Health®: knowledge of a sample of Occupational Physicians and Prevention and Protection Service Managers.

Background: In the workplace, it is increasingly important to promote interventions to improve the work environment that can combine compliance with regulations related to worker health and safety protection with health promotion interventions. The objective of our study is to investigate the status of the implementation of various health management measures through questionnaires submitted to Occupational Physicians (OPs) and Prevention and Protection Service Managers (PPSMs). Methods: This study was conducted between September 2022 and November 2022. Healthcare professionals were invited to voluntarily answer the questions, administered through a Google form, of a standardized questionnaire (Cronbach's alpha=0.887) based on the study made by Hoge et al. (2019): the first part collected demographic information and the other four were relating to the state of implementation of interventions attributable to the Total Worker Health® approach. Results: 89 OPs and PPSMs were involved. The univariate and multivariate analysis shows that, overall, women and PPSMs have a higher degree of dissatisfaction related to various health management measures within companies; most workers are fairly satisfied with health and safety protection in the workplace; finally, according to healthcare professionals, aspects of primary prevention and work management/organization would need to be improved. Conclusions: This study shows that in Italian companies there is often no full application of Total Worker Health® principles. The affirmation of this approach, awareness should be raised, first and foremost, among employers, but also among prevention figures and consultants about all the benefits of Total Worker Health®: one among all, an 'economic' advantage.

Impact of Covid-19 pandemic on injection-based practice: report from an Italian multicenter and multidisciplinary survey.

Background: There are no papers exploring the impact of COVID-19 pandemic on the injection-based practice in patients affected by different rheumatic diseases, including osteoarthritis. The aim was to investigate the impact of COVID-19 pandemic on injection-based practice trough the Italian country. Study design: A survey-based retrospective cross-sectional study. Methods: An Italian-language questionnaire was developed by a group of senior researchers and distributed by e-mail to some Rheumatology, Orthopedic and Rehabilitation Units from different geographic areas of Italy. The survey included information about the number of injections performed during COVID-19 pandemic (stratified by injected agents and injected joint), in comparison to the pre-pandemic period, and the possible reasons behind an eventual reduction. Responses were collected and descriptive analysis calculated. Results: Eleven centers of the National Health Service completed the survey. The activities of the injections services significantly decreased across the country with a percentage of reduction of 60% compared to the pre-pandemic period. A significant reduction of both intra-articular and peri-articular injections was registered. Among intra-articular. treatments, the most affected ones were the hyaluronic acid injections, when compared to corticosteroids. A significant decrease of the total amount of peri-articular injections was observed. The strict government restrictions and the fear of patients to become infected represented the most limiting factors. Conclusions: The reported decrease of the injection-based practice in our country during the COVID-19 pandemic highlights the detrimental effects of the COVID-19 pandemic on the management of chronic musculoskeletal diseases with possible negative consequences in terms of disability and quality of life.

Total neoadjuvant therapy for rectal cancer: Making sense of the results from the RAPIDO and PRODIGE 23 trials.

A few months ago, results from two randomised phase III trials of total neoadjuvant therapy (TNT) in locally advanced rectal cancer were presented (RAPIDO and PRODIGE 23), consistently showing better short- and long-term outcomes with TNT as compared with standard neoadjuvant long-course chemoradiotherapy (CRT) or short-course radiotherapy (SCRT). These results represent corroborating evidence in support of a practice that many centres had already implemented based on promising preliminary data. Also, they provide new, high-level evidence to endorse TNT as a new management option in the treatment algorithm of stage II-III rectal cancer in those centres where CRT and SCRT have long remained the only accepted standard neoadjuvant treatments. Having two consistently positive trials is certainly reassuring regarding the potential of TNT as a general treatment approach. Nevertheless, substantial differences between these trials pose important challenges in relation to the generalisability and applicability of their results, and translation of the same into practical clinical recommendations. In this article, we address a number of key questions that the RAPIDO and PRODIGE 23 trials have raised among the broad community of gastrointestinal oncologists, proposing an interpretation of the data that may help the decision making, and highlighting grey areas that warrant further investigation.

Novel directions in the study of osteoporosis: focus on gut microbiota as a potential therapeutic target.

Osteoporosis is a significant social health problem, not only in terms of pain and disability but also in terms of mortality rate. In recent years, there is an increasing interest in studying the relationship between gut dysmicrobiosis, immune system and bone health, therefore the term "osteomicrobiology" has been recently coined. This review aims to summarize the current knowledge about the link between gut dysbiosis and osteoporosis, in order to define a potential preventive and therapeutic strategy. Gut microbiota (GM) plays a major role in maintaining body homeostasis, since it is involved in several physiological processes; in recent years, the gut microbiota has shown to modulate not only local processes but also systemic responses including bone metabolism. Several potential mechanisms may explain how gut microorganisms could affect bone metabolism, i.e. influencing the host metabolism, immune system and hormone secretion. The relationship between gut dysbiosis, immunological dysfunction and bone loss could be explained by mainly focusing on T cells. Moreover, it should be noted that the relationship between GM and the endocrine system could also explicate how the microbiome influences bone status. In this context, Insulin-Like Growth Factor-1 (IGF-1), vitamin D, serotonin and leptin might play a central role. GM could have a significant impact on bone metabolism, therefore future clinical studies are necessary to develop a new multidisciplinary approach for osteoporosis treatment and prevention.

The limits and potentials of presepsin in orthopaedic surgery: state of the art and future directions.

Presepsin, i.e. the soluble cluster of differentiation 14-SubType (sCD14-ST), is an emerging biomarker for the diagnosis and evaluation of sepsis and infection. In 2004, Yaegashi et al. originally described presepsin as a potential biomarker; since then, several studies have investigated the role of presepsin in different infectious conditions, including neonatal sepsis, severe acute pancreatitis, infections in patients with haematological malignancies, severe community-acquired pneumonia, pacemaker and implantable cardioverter-defibrillator (ICD) pocket infections, surgical site infections (SSIs) and periprosthetic joint infects (PJIs). Moreover, presepsin has been also studied in the risk stratification in cardiac surgery patients, and as a biomarker in the perioperative management of patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). This review aims to summarize the current knowledge about presepsin, focusing on the limits and potentials that the use of this biomarker could have in daily clinical practice. Presepsin is could be useful in daily clinical practice in orthopaedic surgery in the diagnosis and prevention of SSIs and PJIs. It is a cost-effective biomarker, but to improve its accuracy, it is important to carefully recalculate presepsin circulating values in patients with chronic kidney disease. However, further studies with larger patients' samples are needed to better validate the use of this biomarker in orthopaedics. In the future, synovial fluid presepsin might be a useful biomarker in the diagnosis of septic arthritis and PJIs.

Humeral shaft butterfly fractures managed with intramedullary nail: could the third fragment features predict the fracture healing time?

To assess the impact of the radiological features of the third fragment on the outcome of humeral shaft fractures type 12-B managed with endomedullary nails. We retrospectively evaluated a series of 80 patients, divided into 3 groups, according to the fracture healing time: within 6 months (group-A), between 6 and 12 months (group-B) or fracture non-union after 12 months (group-C). In 26 patients out of 80 the fracture healing was observed at 6 months follow-up; in 47 out of 80 at 12 months after trauma and in 7 out of 80 no fracture healing was observed at 12 months follow-up. Regression analysis showed that the third fragment displacement and angulation are the most important features that affect the fracture healing. The mean third fragment dislocation (cut-off: 12 mm) is the main parameter to influence the fracture healing within or in more than six months.

Adjuvant chemotherapy for rectal cancer: Current evidence and recommendations for clinical practice.

While adjuvant chemotherapy is an established treatment for pathological stage II and especially stage III colon cancer, its role in the multimodal management of rectal cancer remains controversial. As a result, there is substantial variation in the use of this treatment in clinical practice. Even among centres and physicians who consider adjuvant chemotherapy as a standard treatment, notable heterogeneity exists with regard to patient selection criteria and chemotherapy regimens. The controversy around this topic is confirmed by the lack of full consensus among national and international clinical guidelines. While most of the clinical trials do not support the contention that adjuvant chemotherapy may improve survival outcomes if pre-operative (chemo)radiotherapy is also given, these suffer from many limitations that preclude drawing definitive conclusions. Nevertheless, in the era of evidence-based medicine, physicians should be guided by the available data and refrain from extrapolating results of adjuvant colon cancer trials to inform treatment decisions for rectal cancer. Patients should be informed of the evidence gap, be given the opportunity to carefully discuss pros and cons of all the possible management options and be empowered in the decision making. In this article we review the available evidence on adjuvant chemotherapy for rectal cancer and propose a risk-adapted decisional algorithm that largely relies on informed patient preferences.

Grey areas and evidence gaps in the management of rectal cancer as revealed by comparing recommendations from clinical guidelines.

BACKGROUND: While the management of nonmetastatic and oligometastatic rectal cancer has rapidly evolved over the last few decades, many grey areas and highly debated topics remain that foster significant variation in clinical practice. We aimed to identify controversial points and evidence gaps in this disease setting by systematically comparing recommendations from national and international clinical guidelines. METHODS: Twenty-six clinical questions reflecting practical challenges in the routine management of nonmetastatic and oligometastatic rectal cancer patients were selected. Recommendations from the ESMO, NCCN, JSCCR, Australian and Ontario guidelines were extrapolated and compared using a 4-tier classification system (i.e., identical/very similar, similar, slightly different, different). Overall agreement between guidelines (i.e., substantial/complete disagreement, partial disagreement, partial agreement, substantial/complete agreement) was assessed for each clinical question and compared against the highest level of available evidence by using the χ2 statistic test. RESULTS: Guidelines were in substantial/complete agreement, partial agreement, partial disagreement, and substantial/complete disagreement for 8 (30.8%), 2 (7.7%), 7 (26.9%), and 9 (34.6%) clinical questions, respectively. High level of evidence supported clinical recommendations in 3/10 cases (30%) where guidelines were in agreement and in 10/16 cases (62.5%) where guidelines were in disagreement (χ2 = 2.6, p = 0.106). Agreement was frequently reached for questions regarding diagnosis, staging, and radiology/pathology pro-forma reporting, while disagreement characterised most of the treatment-related topics. CONCLUSIONS: Substantial variation exists across clinical guidelines in the recommendations for the management of nonmetastatic and oligometastatic rectal cancer. This variation is only partly explained by the lack of supporting, high-level evidence.

Evaluation of long-term postoperative outcomes between mini-open and arthroscopic repair for isolated supraspinatus tears: a retrospective analysis.

BACKGROUND: Despite arthroscopic repair of the rotator cuff is an increasingly popular procedure, the mini-open (MO) repair still remains a viable and appreciated technique. The purpose of the study was to analyze the long-term clinical outcomes of patients with isolated supraspinatus tear undergoing MO or arthroscopic surgery (AS) repair. PATIENTS AND METHODS: Forty-six patients underwent supraspinatus repair with anchors: 24 with MO technique and 22 with AS procedure. They were evaluated postoperatively at 3, 6, 12 months and 2 years. RESULTS: The mean surgery time, the mean hospital stay and the average costs were shorter in the MO patients respect to the AS group. Despite an initial better Disabilities of Arm, Shoulder and Hand and Constant Murley Score in the first 6 months of follow-up in the AS group, no differences were detected at 24 months. CONCLUSION: This study suggests that isolated supraspinatus tears can be treated with a MO or arthroscopic repair procedure with similar clinical outcome in the long-term postoperative period. The mean surgery time and the average costs are less in the MO group respect to the AS group.

The Boltzmann project.

The International Committee for Weights and Measures (CIPM), at its meeting in October 2017, followed the recommendation of the Consultative Committee for Units (CCU) on the redefinition of the kilogram, ampere, kelvin and mole. For the redefinition of the kelvin, the Boltzmann constant will be fixed with the numerical value 1.380 649 × 10-23 J K-1. The relative standard uncertainty to be transferred to the thermodynamic temperature value of the triple point of water will be 3.7 × 10-7, corresponding to an uncertainty in temperature of 0.10 mK, sufficiently low for all practical purposes. With the redefinition of the kelvin, the broad research activities of the temperature community on the determination of the Boltzmann constant have been very successfully completed. In the following, a review of the determinations of the Boltzmann constant k, important for the new definition of the kelvin and performed in the last decade, is given.

Autologous lipotransfer versus stromal vascular fraction enriched lipoinjection for diabetic foot wounds healing: a pilot study.

Chronic ulcers of the lower limbs represent a significant social and economic burden. Diabetes is a strong risk factor for development of chronic lesions. Adult stem cells and growth factors derived from the adipose tissue are among the most promising therapeutic strategies for hard to heal wounds. Fat grafts have been used for several decades to treat soft tissue deformities, but despite its excellent characteristics, the outcome was unpredictable, due to partial necrosis and resorption of the graft. Stem cells' enrichment of these grafts or their injection into the edges of the ulcers have shown encouraging results in various experimental settings. In this pilot study, we compared the standard of care to autologous lipotransfer and stromal vascular fraction (SVF) enriched lipoinjection in 30 patients with diabetic foot ulcers, showing clear superiority of SVF enriched lipoinjection in terms of percentage of reduction of ulcers size and healing time.

Irisin levels correlate with bone mineral density in soccer players.

Irisin, a novel myokine produced in response to physical exercise by skeletal muscle, displays anabolic effect on bone and can improve the bone-loss-induced osteoporosis in hind limb suspended mice. It is well known that muscles positively impact the skeleton and in different sports, including soccer, total body bone mineral density (TB-BMD) is elevated. Therefore, we have investigated the correlation between irisin serum levels and total and bone sub-regional BMD in soccer players never studied before. In this study, Caucasian football players of Bari team have been enrolled. Their sera were collected to measure by ELISA kit irisin levels and by dual-energy X-ray absorptiometry (DEXA) analysis measurements of BMD (g • cm−2) in the whole body and different bone sub-regions (head, arms, legs, ribs, dorsal vertebrae, lumbar vertebrae, pelvis) were performed. The BMC (g) was measured in the whole body. By means of Pearson's (R) and Cohen's (d) coefficient we investigated the linear association between the irisin serum levels and BMD. In soccer players, we have found a positive correlation between irisin and TB-BMD as demonstrated by the values of Pearson and Cohen's (d) coefficient. Furthermore, linear association was detected between irisin and BMD of different bone-site such as right arm, lumbar vertebrae and head. A positive trend was also observed analyzing circulating levels of irisin and bone mineral content as well as total Z-score. In conclusion, we have demonstrated the correlation between irisin and total or bone sub-regional BMD in soccer players for the first time, an additional systemic effect of the "sport-hormone" defined myokine.