Real-life use of ropeg-interferon α2b in polycythemia vera: patient selection and clinical outcomes.

Ropeginterferon-alfa2b (ropegIFNα2b) is a long-acting IFN formulation with broad FDA/EMA approval as a therapy of polycythemia vera (PV) with no symptomatic splenomegaly. There is currently lack of information on the real-world patient selection, including the impact of local reimbursement policies, and drug management, particularly: type/timing of screening and follow-up tests; absolute/relative contraindications to therapy; ropegIFNα2b dose and combinations with hydroxyurea. As a sub-analysis of the PV-ARC retrospective study (NCT06134102), we here report our monocenter experience with ropegIFNα2b in the period from January 2021, corresponding to drug availability outside clinical trial, and December 2023. Among the 149 patients with EMA/FDA indication, only 55 (36.9%) met the local reimbursement criteria and 18 (12.1%) received ropegIFNα2b. Thanks to appropriate screening, relative/absolute contraindications to ropegIFNα2b were detected and managed in a multidisciplinary manner. Efficacy and safety of ropegIFNα2b was confirmed, with 3 cases of early molecular response. General use of low ropegIFNα2b dose, with frequent need for hydroxyurea combinations, was noted. This real-world experience suggests a significant impact of local regulations on drug prescription and the need for greater real-world data collection on ropegIFNα2b in PV patients. Also, it describes appropriate multidisciplinary screening and monitoring procedures during ropegIFNα2b therapy.

Perioperative dental screening and treatment in patients undergoing cardiothoracic surgery and interventional cardiovascular procedures. A consensus report based on RAND/UCLA methodology.

AIM: To reach a consensus on a consistent strategy to adopt when screening patients for dental/periodontal infections and on the feasibility of providing dental treatment before cardiothoracic surgery, cardiovascular surgery or other cardiovascular invasive procedures. METHODOLOGY: A panel of experts from six Italian scientific societies was created. The deliberations of the panel were based on the RAND method. From an initial systematic literature review, it became clear that a consensually validated protocol for the reproducible dental screening of patients awaiting cardiac interventions was considered mandatory by professionals with expertise in the dental, cardiologic and cardiac surgery areas. However, a systematic review also concluded that the treatment options to be provided, their prognosis and timing in relation to the physical condition of patients, had never been defined. Following the systematic review, several fundamental questions were generated. The panel was divided into two working groups each of which produced documents that addressed the topic and which were subsequently used to generate a questionnaire. Each member of the panel completed the questionnaire independently, and then, a panel discussion was held to reach a consensus on how best to manage patients with dental/periodontal infections who were awaiting invasive cardiac procedures. RESULTS: A high level of agreement was reached regarding all the items on the questionnaire, and each of the clinical questions formulated were answered. Three tables were created which can be used to generate a useful tool to provide standardized dental/periodontal screening of patients undergoing elective cardiovascular interventions and to summarize both the possible oral and cardiovascular conditions of the patient and the timing available for the procedures considered. CONCLUSIONS: Upon publication of this consensus document, the dissemination of the information to a wide dental and cardiac audience should commence. The authors hope that this consensus will become a model for the development of a dedicated protocol, ideally usable by heart and dental teams in the pre-interventional preparation phase.

Perioperative dental screening and treatment in patients undergoing cardio-thoracic surgery and interventional cardiovascular procedures. A consensus report based on RAND/UCLA methodology.

AIM: To reach a consensus on a consistent strategy to adopt when screening patients for dental/periodontal infections, and on the feasibility of providing dental treatment before cardiothoracic surgery, cardiovascular surgery or other cardiovascular invasive procedures. METHODOLOGY: A panel of experts from six Italian scientific societies was created. The deliberations of the panel were based on the RAND method. From an initial systematic literature review, it became clear that a consensually validated protocol for the reproducible dental screening of patients awaiting cardiac interventions was considered mandatory by professionals with expertise in the dental, cardiologic and cardiac surgery areas. However, systematic review also concluded that the treatment options to be provided, their prognosis and timing in relation to the physical condition of patients had never been defined. Following the systematic review several fundamental questions were generated. The panel was divided into two working groups each of which produced documents that addressed the topic and which were subsequently used to generate a questionnaire. Each member of the panel completed the questionnaire independently and then a panel discussion was held to reach a consensus on how best to manage patients with dental/periodontal infections who were awaiting invasive cardiac procedures. RESULTS: A high level of agreement was reached regarding all the items on the questionnaire, and each of the clinical questions formulated were answered. Three tables were created which can be used to generate a useful tool to provide standardized dental/periodontal screening of patients undergoing elective cardiovascular interventions, and to summarize both the possible oral and cardiovascular conditions of the patient and the timing available for the procedures considered. CONCLUSIONS: Upon publication of this consensus document, the dissemination of the information to a wide dental and cardiac audience should commence. The authors hope that this consensus can become a model for the development of a dedicated protocol, ideally usable by heart and dental teams in the pre-interventional preparation phase.

Zr, Hf and REE distribution in river water under different ionic strength conditions.

The Platani River flowing in south-central Sicily, interacting with evaporite rocks, generates a wide range of ionic strength in the water catchment from 0.1 to 5.0molkg-1. We sampled 38 river sites and analysed the composition for the dissolved fraction filtered through 0.45µm, the truly dissolved fraction obtained through ultrafiltration (10kDa) and the relative included colloidal fraction. This study was focused on the recognition of Zr, Hf and REE behaviour under changing ionic strength conditions, since this is one of parameters responsible for colloid stability in natural waters. In turn, this phenomenon leads to REE release from the colloidal fraction and their scavenging onto surfaces of suspended particles or sediment, or their complexation with dissolved ligands. Our results indicated that in both dissolved and ultra-filtrated fractions REE increases either in the middle (Sm - Dy) or in the heavier (Ho - Lu) part of the PAAS-normalised distribution, while the Zr/Hf ratio value ranges from sub-chondritic to super-chondritic. Scanning Electron Microscopic and Energy Dispersive X-ray Spectrometric (SEM-EDS) analyses and dissolved Mg, Al and Fe concentrations suggested that the studied colloids consist of aggregations of Al-oxyhydroxides, carbonate nanoparticles and clays where organic traces were not found. The studied colloids showed greater affinity with dissolved Zr than Hf determining Zr/Hf values larger than the chondritic values. The largest Zr/Hf values were found in colloidal fractions from waters with ionic strength larger than 0.6molkg-1. These Zr/Hf values up to 280 (w/w) are provided by the faster removal of Hf relative to Zr from coagulating colloids and its preferential scavenging onto authigenic Fe-oxyhydroxides in bottom sediment. Further studies are needed to clarify is this suggested process can represent a suitable starting point for the Zr-Hf decoupling observed in seawater.

Bullous morphoea: a retrospective study.

Bullous morphoea is a rare variant of localized scleroderma whose pathogenesis has been widely discussed. We retrospectively reviewed the records of all histopathologically confirmed cases of morphoea followed from 2005 to 2015 at the Dermatology Clinic and Pathology Institute of the University of Cagliari, Sardinia, Italy. Among 137 patients with morphoea, 2 cases of the bullous variant were identified, which were successfully treated with methotrexate. Thus, the bullous form comprised 1.4% of all cases of morphoea, which is much lower than the 7.5% previously reported. In one of the cases, histopathological examination revealed a peculiar 'stretching' pattern of basal keratinocytes attached to the epidermal roof of the bulla, together with increased lymphatic vessels, which were either collapsed or dilated, stressing the role of lymphatics and possibly of excessive skin trauma and friction in the development of bullous lesions.

Robot-assisted gait training improves motor performances and modifies Motor Unit firing in poststroke patients.

BACKGROUND: Robotics and related technologies are realizing their promise to improve the delivery of rehabilitation therapy but the mechanism by which they enhance recovery is still unknown. The electromechanical-driven gait orthosis Lokomat has demonstrated its utility for gait rehabilitation after stroke. AIM: To test the efficacy of Lokomat in gait retraining and to investigate the neurophysiological mechanisms underlying the recovery process. DESIGN: Case series study. SETTING: Unit of Neurorehabilitation of a University Hospital. POPULATION: Fifteen patients with post-stroke hemiparesis. METHODS: Patients underwent a six weeks rehabilitative treatment provided by Lokomat. The outcome measures were: Fugl-Meyer Motor Scale (FMMS), Berg Balance Scale (BBS), 10 metres Walking Test (10mWT), Timed Up and Go test (TUG), 6 Minute Walking Test (6MWT). Strength and Motor Unit firing rate of vastus medialis (VM) were analyzed during isometric knee extension through an isokinetic dynamometer and surface EMG recording. RESULTS: An increase of duration and covered distance, a decrease of body weight support and guidance force on the paretic side along the sessions were observed. The FMMS, the BBS, the TUG and the 6MWT demonstrated a significant improvement after the training. No increase of force was observed whereas a significant increase of firing rate of VM was recorded. CONCLUSION: The evidence that the improvement of walking ability observed in our study determines a significant increase of firing rate of VM not accompanied by an increase of force could suggest an effect of training on motorneuronal firing rate that thus contributes to improve motor control. CLINICAL REHABILITATION IMPACT: Given the current wide use of robotics in gait retraining after stroke, our approach can contribute to clarify the mechanisms underlying its rehabilitative impact so as to incorporate the findings of evidence-based practice into appropriate treatment plans for persons poststroke.

Benefits of an intensive task-oriented circuit training in Multiple Sclerosis patients with mild disability.

BACKGROUND: Exercise is well tolerated and induces relevant improvements in physical and mental functioning of persons with Multiple Sclerosis (MS). Unfortunately, due to the wide variety of symptoms and the broad range of exercise interventions, it is not possible to make unified exercise recommendation as to what type of exercise is safe and effective for persons with MS. OBJECTIVE: The aim was to test the impact of an intensive task-oriented training on motor function and quality of life in 17 MS patients with an Expanded Disability Status Scale (EDSS) between 4 and 5.5. METHODS: Patients underwent a two-week intensive, task-oriented rehabilitation program. Outcome measures were: Berg Balance Scale, Gait Dynamic Index, 6 Minute Walking Test, Physiological Cost Index, Fatigue Severity Scale, 10 metres Walking Test, Timed Up and Go test, Short form 36, Multiple Sclerosis Impact Scale, Patient Health Questionnaire. RESULTS: All outcome measures showed a significant improvement after the treatment except for the 6 Minute Walking test and the Short form 36 that showed a trend of improvement although not statistically significant. CONCLUSIONS: An intensive task-oriented rehabilitation protocol is effective in improving motor function and has a positive impact on quality of life in MS patients with moderate disability.

Nail dystrophies, scalp and intergluteal/perianal psoriatic lesions: risk factors for psoriatic arthritis in mild skin psoriasis?

AIM: In the literature, clinical features of psoriasis associated with psoriatic arthritis (PsA) onset have not been clarified, even if high Psoriasis Area and Severity Index (PASI) was found to be directly related with PsA. METHODS: The study was conducted between November 2008 and April 2009 on consecutive psoriatic outpatients referred to a service of dermatological consultations, on indication of other hospital specialists. Participants were affected by mild skin psoriasis, in particular with nail dystrophies and/or scalp and/or intergluteal/perianal lesions. The questionnaire provided by the Classification of Psoriatic Arthritis (CASPAR) study group was proposed to all patients and we added a question about the time of psoriasis onset. RESULTS: Eighty-seven subjects (34 males and 53 females) aged between 18 and 91 years (mean age 48 years) with such psoriatic features were recruited. Other 30 refused to take part to the study. Forty-seven per cent of these participants were found to suffer from PsA, in particular 83% of those with nail and scalp psoriasis, 40% of subjects with intergluteal/perianal involvement and 37% of patients with just scalp lesions. We present the first exploratory and observational study focused on a population with mild skin psoriasis, in order to evaluate if nail dystrophies, scalp or intergluteal/perianal psoriatic lesions might be indicative of a higher risk of PsA even in cases with mild skin psoriasis. CONCLUSION: Nail psoriasis is probably a suggestive feature of joint involvement. The scalp psoriasis, as well as intergluteal/perianal psoriatic lesions, is likely to be less associated to PsA, but may be an important comorbidity factor for the development of PsA. Further investigations in a larger population are encouraged to assess a potential link between PsA, site-specific and mild skin psoriasis.

Periungual pyogenic granulomas due to topical tazarotene for nail psoriasis.

Tazarotene is a topically-applied, receptor-selective retinoid that has been shown to modulate several major pathogenic factors of psoriasis. Adverse effects are those of topical application of retinoids, the most common being mild to moderate burning, itching, stinging, and erythema, due to mild to moderate local skin irritation. While pyogenic granuloma-like lesions are a well recognized side effects of systemic retinoids, to our knowledge in the literature there is only one reported case of pyogenic granuloma (PG) following topical application of tazarotene for scalp psoriasis. In this paper we report 2 cases of periungual PGs following application of topical tazarotene and we present a review of the literature.

Abnormal lactate levels in patients with polymyositis and dermatomyositis: the benefits of a specific rehabilitative program.

BACKGROUND: Polymyositis (PM) and Dermatomyositis (DM) are chronic, inflammatory and autoimmune skeletal muscle disorders characterized by reduced muscle strength, fatigue and myalgia. While inflammation causes muscle damage in the early phase, metabolic alterations such as an impairment of oxidative metabolism seem to be responsible for the disability in the chronic phase of the disease. AIM: To assess muscle oxidative efficiency and to test the effect of aerobic training in a group of PM/DM patients. DESIGN: A case-control study and a within-group comparison. SETTING. Outpatients of the Unit of Neurorehabilitation of the University Hospital of Pisa. POPULATION: 20 patients with myositis (15 PM and 5 DM) and 15 healthy subjects as a control group. METHODS: The test consisted of an incremental, sub-maximal aerobic exercise on a treadmill; haematic lactate was assessed at rest and after 1', 5', 10' and 30' minutes from the end of the exercise. A within-group comparison was conducted on four of the PM patients (P group). They were subjected to six weeks aerobic training. Lactate curve and functional tests were assessed before and after the treatment. RESULTS: A precocious fatigability and significantly higher values of lactate at rest and after the exercise were observed in patients. In the P group mean lactate levels were significantly decreased after the treatment and an improvement of muscle performance was observed. CONCLUSION: Abnormal blood lactate levels suggested an impaired muscle oxidative efficiency in PM/DM patients. A specific aerobic training program reduced lactate levels and relieved fatigue symptoms in a within-group of four of the PM patients. CLINICAL REHABILITATION IMPACT: Such a specific aerobic training program could be introduced in everyday practice for the rehabilitative treatment of PM/DM patients.

A novel bispecific EGFR/Met antibody blocks tumor-promoting phenotypic effects induced by resistance to EGFR inhibition and has potent antitumor activity.

Simultaneous targeting of epidermal growth factor receptor (EGFR) and Met in cancer therapy is under pre-clinical and clinical evaluation. Here, we report the finding that treatment with EGFR inhibitors of various tumor cells, when stimulated with hepatocyte growth factor (HGF) and EGF, results in transient upregulation of phosphorylated AKT. Furthermore, EGFR inhibition in this setting stimulates a pro-invasive phenotype as assessed in Matrigel-based assays. Simultaneous treatment with AKT and EGFR inhibitors abrogates this invasive growth, hence functionally linking signaling and phenotype. This observation implies that during treatment of tumors a balanced ratio of EGFR and Met inhibition is required. To address this, we designed a bispecific antibody targeting EGFR and Met, which has the advantage of a fixed 2:1 stoichiometry. This bispecific antibody inhibits proliferation in tumor cell cultures and co-cultures with fibroblasts in an additive manner compared with treatment with both single agents. In addition, cell migration assays reveal a higher potency of the bispecific antibody in comparison with the antibodies' combination at low doses. We demonstrate that the bispecific antibody inhibits invasive growth, which is specifically observed with cetuximab. Finally, the bispecific antibody potently inhibits tumor growth in a non-small cell lung cancer xenograft model bearing a strong autocrine HGF-loop. Together, our findings strongly support a combination treatment of EGFR and Met inhibitors and further evaluation of resistance mechanisms to EGFR inhibition in the context of active Met signaling.

Trans-obturator colonic suspension during Altemeier's operation for full-thickness rectal prolapse: preliminary results with a new technique.

AIM: With the aim of reducing recurrence after perineal surgery for full-thickness rectal prolapse, a new operation consisting of a trans-obturator colonic suspension during Altemeier's operation has been developed. METHOD: Eighteen women with full-thickness rectal prolapse were examined clinically, with validated quality of life and continence scores, colonoscopy, anorectal manometry, anal EMG and sacral reflex latency. Ten had a newly diagnosed and eight a recurrent prolapse. The Altemeier operation was combined with a levatorplasty in all cases using two porcine collagen prostheses sutured to the descending colon and passed through the trans-obturator space bilaterally. The operation was completed by a manual or stapled colo-anal anastomosis. Clinical examination, with quality of life and continence scores, anorectal manometry, EMG and sacral reflex latency, was scheduled during follow up, with the recurrence of prolapse as the primary outcome measure. RESULTS: There were no recurrences at 30 months. There was no mortality and no complications. All patients experienced significant improvement in quality of life and faecal continence scores (P<0.01). Surgery did not affect anorectal pressures or sacral reflex latencies. CONCLUSION: The new technique appears to be relatively easy to perform and is complication free with no recurrence after a short period of follow up. A larger study with appropriate controls and longer follow up is now needed to assess its real effectiveness in reducing the risk of recurrence.

Immunohistochemical expression of p16(INK4A) protein in oral lichen planus.

The expression of p16(INK4A) has been investigated in oral leukoplakias (OLK), but no data are available about oral lichen planus (OLP). In this study, p16(INK4A) immunohistochemical expression was evaluated in 56 OLP and 36 OLK (12 without inflammation [NI-OLK] and 24 with chronic inflammation [I-OLK]) and compared with 23 reactive nonspecific inflammations (INF) and 14 normal control samples. The p16(INK4A) immunostaining was considered to be positive when >5% of keratinocytes were stained. All normal control samples were negative. Positive p16(INK4A) was detected in OLP, IOLK, and INF. Significant differences in p16(INK4A) positivity were found between OLP (64%) and OLK (28%) (χ(2) = 17.7; P < .01), and between I-OLK and NI-OLK (χ(2) = 4.5; P < .05). No significant difference was found between OLP and INF (43%). In conclusion, positive p16(INK4A) in OLP patients seems to be related to reactive inflammatory processes rather than to a risk of progression to oral squamous cell carcinoma.

Low-grade myofibroblastic sarcoma of the gingiva.

Low-grade myofibroblastic sarcoma is a malignant tumour from myofibroblasts, which has only recently become clearly defined. It represents a rare entity developing in the soft tissues of the head and neck. About 20 cases have been reported in the oral cavity, especially in the tongue and bone, while gingiva as the primary site has been described only once to date. Diagnostic methods include histology and immunohistochemistry. The present report concerns a case of a 37-year-old man who presented with a persistent gingival ulcerated swelling that was interpreted for a long time as a gingival epulis. A low-grade myofibrosarcoma was diagnosed and the patient underwent a segmental osteotomy of the mandibular symphisys for complete excision. There was no sign of recurrence or metastatic disease during the 18-month postoperative period.

Tuberculosis teaching in Brazilian medical schools.

To achieve tuberculosis (TB) control, National Tuberculosis Programme guidelines should be implemented effectively. In a survey conducted in 2005-2006, 33 Brazilian medical school coordinators answered a questionnaire about TB education. The median time dedicated to TB was 27 h (4-119 h), spread over several disciplines, mainly biological and clinical. This included 12 h (0-88 h) of practical activities, mainly in university hospitals (53%). The recommendation to offer human immunodeficiency virus testing for TB patients was taught in only 54% of the schools. TB education in Brazil is fragmented and restricted to a biological approach, while field activities are insufficient and carried out in inadequate settings. Important changes to the TB curriculum are necessary.

A comparison between two electronic apex locators: an ex vivo investigation.

AIM: To compare ex vivo the performance of the Apex Finder and the Root ZX apex locators, with and without irrigant, in canals having different diameters. METHODOLOGY: Sixty canals in 60 teeth were prepared using stainless steel hand files and 0.04 taper NiTi rotary instruments. During preparation the narrowest diameter of the canal was transported to the apical root surface. The canals were irrigated with RC-Prep and 5% NaOCl solution. Six groups were obtained, each with 10 canals having the same diameter of foramen, either 0.15, 0.20, 0.25, 0.40, 0.60 and 0.80 mm. A size 15 K-file was advanced into each canal until its tip was observed under x10 magnification to reach the foramen and the corresponding length recorded. The measurements were performed to an accuracy of 0.25 mm as a base unit of length. The teeth were then fixed to a plastic bar suspended over a glass container filled with 0.9% NaCl solution. Each apex locator was tested when the K-file was at the foramen, or 0.5, 1.0, 1.5 and 2.0 mm short; with the root apex immersed into the solution; with the canal dry or irrigated with NaCl. To evaluate the accuracy of both electronic apex locators (EALs) each electronically determined distance was compared with the actual length and the data analysed using the General Linear Model and the Student t-test. RESULTS: Out of 2400 measurements 100 were electrically unstable, all with the Root ZX. In total, 521 measurements located the position of the file tip beyond the apex, in general, in high conductive conditions with the Root ZX and in low conductive conditions with the Apex Finder. No significant difference in terms of accuracy was found between the two EALs when the file tip was at the foramen (Root ZX mean +0.12 mm, SD 1.22 mm; Apex Finder mean +0.57 mm, SD 1.16 mm). Comparing all the measurements performed with the file tip within 2 mm of the foramen, in all the different conditions tested, the accuracy was affected (P<0.025) by diameter of the foramen, type of EAL, distance to the apex, and by several interactions. CONCLUSIONS: Under the different ex vivo conditions both EALs provided accurate measurements when the file tip was at the foramen. The accuracy of the Apex Finder was negatively influenced by high conductive conditions, whilst the Root ZX provided inaccurate and unstable measurements mostly in low conductive conditions.

An ex vivo comparison of three different gutta-percha cones when compacted at different temperatures: rheological considerations in relation to the filling of lateral canals.

AIM: To compare ex vivo the penetration of three brands of gutta-percha cones, compacted under a constant force and heated to different temperatures, into artificial lateral canals. METHODOLOGY: Resin blocks with simulated main canals, each having two lateral canals (C at 6.5 and A at 13 mm from the surface of the resin block), were selected. A gutta-percha cone, either Mynol MF, Hygenic MF or GT Tulsa 0.04 was compacted into each main canal for 5 s using a wire rod with a diameter of 0.7 mm soldered to the bottom of a metal cylinder, with a force of 2.7 kg at controlled temperatures of 37, 42, 47, 52, 60 degrees C. The penetration of each brand of gutta-percha into 60 lateral canals (10 at each temperature) was measured using a stereomicroscope. Statistical analysis was performed using the ANOVA, the Scheffè test and the t-test. RESULTS: None of the three brands of cones entered up to 0.1 mm within either lateral canal until a temperature of 47 degrees C was reached; at that temperature only Mynol cones (P < or = 0.05) penetrated in four of 10 A-level canals (mean 0.13 +/- 0.19 mm) and in all 10 C-level canals (mean 0.43 +/- 0.12 mm). The A-level lateral canals were penetrated at 52 degrees C by Mynol cones (mean 0.76 +/- 0.34 mm) to a significantly greater distance (P < or = 0.05) than Tulsa cones (mean 0.31 +/- 0.12 mm) and Hygenic cones (mean 0.11 +/- 0.08 mm). At 60 degrees C the Mynol cones (mean 1.93 +/- 0.34 mm) penetrated significantly more (P < or = 0.05) than the Tulsa cones (mean 0.86 +/- 0.22 mm) and Hygenic cones (mean 0.67 +/- 0.19 mm). The C-level lateral canals were penetrated at 52 degrees C by Mynol cones (mean 0.91 +/- 0.29 mm) to a significantly greater distance (P < or = 0.05) than Tulsa cones (mean 0.47 +/- 0.16 mm) and Hygenic cones (mean 0.46 +/- 0.15 mm), whilst no significant difference was found at 60 degrees C. CONCLUSIONS: When heated and compacted, the three gutta-percha cones penetrated the lateral canals to different degrees. They penetrated more than 0.43 mm into the lateral canals only at temperatures higher than 47 degrees C.