Alternate use of thrombopoietin receptor agonists in adult primary immune thrombocytopenia patients: A retrospective collaborative survey from Italian hematology centers

Sequential use of the TPO‐RAs romiplostim and eltrombopag in ITP patients failing either agent was retrospectively evaluated to assess efficacy and impact of clinical characteristics on outcome. Patients were grouped into 5 categories: efficacy issues: 1^st TPO‐RA failure; loss of response; non‐efficacy issues: platelet fluctuations; patient's preference; adverse event development. Either one TPO‐RA sequence was analyzed at 3 month and at last follow‐up. 106/546 patients on TPO‐RA underwent switch and 65% achieved, regained or maintained a short‐ term response independent of switch sequence, gender or age; lower response rates were associated with lines of previous therapy; disease duration lowers probability to respond. Clinically, patients switched for efficacy issue did not differ from those switched for non‐efficacy issues. Response was achieved/regained in 57.8% of patients switched for efficacy issues, the lowest response rates were observed in non‐responders to 1^st TPO‐RA; 80% of patients switched for non‐efficacy issues maintained a response. Platelet fluctuation resolved in 44.4%. Of the 49 patients evaluable for long‐term outcome, 27 were in response on therapy; 16 discontinued the TPO‐RA for reasons other than efficacy, while only 6 were non responders. We confirm the efficacy of TPO‐RA switch; once achieved, response to the 2^nd TPO‐RA seems durable.     

The Italian validation of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS) and the application of the Cognitive Impairment Index scoring procedure in MS patients

Cognitive dysfunction occurs in almost 50–60% of patients with multiple sclerosis (MS) even in early stages of the disease and affects different aspects of patient’s life. Aims of the present study were (1) to introduce and validate an Italian version of the minimal assessment of cognitive functions in MS (MACFIMS) battery and (2) to propose the use of the Cognitive Impairment Index (CII) as a scoring procedure to define the degree of impairment in relapsing-remitting (RRMS) and secondary-progressive (SPMS) patients. A total of 240 HC and 123 MS patients performed the Italian version of the MACFIMS composed by the same tests as the original except for the Paced Auditory Serial Addition Test. The CII was derived for each score of the 11 scales for participants of both groups. The results of the study show that cognitive impairment affects around 50% of our sample of MS patients. In RRMS group, only the 15.7% of patients reported a severe impairment, while in the group of SPMS, the 51.4% of patients felt in the “severely impaired” group. Results are in line with previously reported percentages of impairment in MS patients, showing that the calculation of the CII applied to the Italian version of the MACFIMS is sensitive and reliable in detecting different degrees of impairment in MS patients.     

A new database for ribosomal protein genes which are mutated in Diamond-Blackfan Anemia

Mutations in ribosomal proteins RPS19, RPS24 and RPS17 have been reported in Diamond-Blackfan Anemia (DBA), an autosomal dominant disease characterised by pure red cell aplasia. DBA is the prototype of ribosomapathies: a protein synthesis defect in a tissue with a high cellular turnover is considered the cause of the erythroid progenitor failure. We have created the Diamond-Blackfan Anemia mutation database to curate and record DBA gene mutations, together with their functional consequences and clinical phenotypes. This locus-specific resource is open to future submissions and is available online (http://www.dbagenes.unito.it). It is founded on the Leiden Open (source) Variation Database (LOVD) system and includes data from sequence and structure analysis tools, genomic database resources and published reports. It lists all identified variants and background genomic information. Phenotypic data are accessed by selecting a particular mutation. The database includes 219 unique variants of which 86 are disease-causing mutations. The database will be supplemented with other DBA genes as soon as they are reported and their mutations are identified and it should be of assistance to clinicians and investigators involved in DBA research and care.     

Comparison of three methods for estimating vertical displacement of center of mass during level walking in patients

Three methods of estimating the vertical displacement of the center of mass (COM) during level walking were compared in 30 consecutive patients with gait disability. The methods were: (1) sacral marker method, (2) segmental analysis method and (3) force plate method. The force plate method produced data with a lower range and a different distribution than the other two methods. There was no significant difference between the data of the sacral marker and segmental analysis methods (Johnson's modified t-test, P = 0.16). These two methods are likely more accurate and sensitive methods of estimating the changes in the vertical displacement of COM than the force plate method. The segmental analysis method is prone to errors because the model and anthropometric estimations used may not be applicable to every patient. The sacral marker method is a simple, inexpensive, effective and accurate tool to estimate the vertical displacement of the COM.     

New Technique for Retrograde Cerebral Perfusion During Arch Aneurysm Repair

Many techniques are used to reduce brain damage during surgery for dissecting aneurysms of the ascending aorta and arch. Recently, new techniques of protection were proposed, consistent with hypothermic circulatory arrest in association with retrograde cerebral perfusion via superior vena cava. We propose a simple, time-saving method, which does not require any manipulation of the heart. We use a multilumen cannula for cardioplegia (D 860-DIDECO FUNDARO') with pressure transducer. This cannula is inserted in superior vena cava by means of a simple purse-string, and linked to the arterial line with a “Y” derivation, allowing retrograde perfusion of the brain and monitoring the perfusion pressure at every moment. The superior vena cava placed downstream from the cannula is closed by a small vascular clamp, to avoid blood reflux in the right atrium. This method is timeand money-saving, is readily available, and can be prepared whenever necessary, also in the middle of the surgical procedure.     

Metal Determination in Organic Fluids of Patients with Stainless Steel Hip Arthroplasty

In 20 stainless steel Charnley hip arthroplasties (with a follow-up of 10-13 years) nickel, chromium and manganese levels were measured in blood, plasma and urine by atomic absorption spectrophotometry. Skin patch tests for these metals, and clinical and roentgenographic results of arthroplasty were also assessed. Metal levels in organic fluids were plotted against a control population homogeneous for age, residence and anamnestic conditions with the first, but which had never undergone a prosthesis or other metallic implant surgical procedure. Nickel levels in blood, plasma and urine, manganese levels in blood and urine and chromium levels in plasma were significantly higher in the hip prostheses population.

Metal ion release from stainless steel prostheses is discussed with regard to implant failure, metal sensitivity and carcinogenesis.     

Il problema dell'eredita' del diabete

Riassunto Una revisione critica di tutti i dati finora disponibili riguardanti la trasmissione ereditaria del diabete, sia conclamato che latente nonchè dello «stato prediabetico», porta alla conclusione che il diabete clinicamente «primitivo» ha un sicuro fondamento genetico e che l'ipotesi che meglio si accorda con i dati predetti è quella di un'eredità multifattoriale. E' probabile che il gene principale interessi la funzione insulare e si trasmetta con un meccanismo di eredità intermedia. I geni accessori potrebbero agire nel senso di favorire il passaggio da una situazione prediabetica a quella diabetica latente o conclamata ciò che è pure condizionato dall'intervento di fattori ambientali.

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Summary A critical review of the till now available data concerning the hereditary transmission of diabetes (in its clear, latent or prediabetes status) induces to the conclusion that the clinically «primitive» diabetes has a reliable genetic ground, and that the hypothesis of a multifactorial heredity agrees with the aforesaid data. It is probable that the main gene affects the insular function and is conveyed by means of an intermediate heredity process. The additional genes could act in promoting the passage from a prediabetic status to a latent or clear diabetes. This passage is conditioned by evironment factors too.

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Zusammenfassung Eine kritische Durchsicht aller bis zum heutigen Tage verfuegbaren Daten ueber die hereditaere Uebertragung des ausgebrochenen sowie des latenten Diabetes und des «praediabetischen Zustandes» fuehrt zu der Schlussfolgerung, dass der klinisch «primitive» Diabetes eine sicherlich genetische Grundlage hat und dass die Hypothese, die am besten mit den vorher gesagten Daten im Einklang steht, die der multifaktorialen Hereditaet ist. Es ist wahrscheinlich, dass das Hauptgen die Inselfunktion interessiert und mit einem Mechanismus intermediaerer Hereditaet uebertragen wird. Die Nebengene koennten in dem Sinne wirken, dass sie die Passage von einer praediabetischen Situation in latenten Diabetes oder offenen Diabetes beguenstigen; dies wird auch durch den Eingriff von Umweltfaktoren bedingt.

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Resumen Una revisión crítica de todos los datos hasta ahora disponibles referentes a la transmisión hereditaria de la diabetes, tanto declarada como latente además del «estado prediabético», lleva a la conclusión que la diabetes clinicamente «primitiva» tiene un seguro fundamento genético y que la hipótesis que mejor se concuerda con los datos antes mencionados es la de una herencia multifactorial. Es posible que el geno principal interese las funciones insulares y se transmita con un mecanismo de herencia intermedia. Los genos accesorios podrían actuar en el sentido de favorecer el pasaje de una situación prediabética a la diabética latente o declarada lo que es también condicionado por la intervención de factores ambientales.

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Resume Une révision critique de tous les données, que nous avons au présent, concernants la transmission héréditaire du diabète, soi déclaré que latent, et de «l'état prédiabétique», nous porte à la conclusion que le diabète cliniquement «primitif» a une base génétique sure et que l'hypothèse qui mieux s'accompagne à ces données, est celle d'une hérédité de plusieurs facteurs. Il est probable que le gêne principal concerne la fonction insulaire et qu'il soit transmis par hérédité intermédiaire. Les gênes accessoires pourraient agir dans le sens de favoriser le passage de une situation prédiabétique à une situation diabétique latente ou déclarée, événement qui est aussi condictionné à l'intervention des facteurs du milieu.

     

Reliability of EMG time-frequency measures of fatigue during repetitive lifting

PURPOSE: To test the short-term and long-term reliability of time-frequency electromyographic (EMG) measures of fatigue during repetitive dynamic lifting and compare it with the reliability of median frequency (MF) EMG measures of fatigue during static lifting. METHODS: Fourteen' healthy male subjects (26 +/- 5 years) repetitively (12 lifts/min) lifted and lowered a box (29 x 25 x 23 cm, 13 kg) for 4.5 min during 3 different tests on 2 different days. EMG data and the biomechanics of motion were recorded. Before and after dynamic lifting, static maximum lifting tests were performed. At the end of each of the two sessions, subjects performed a static lift at 80% of their maximum lifting force for 30 s. RESULTS: Significant fatigue-related changes were observed during the lifting exercise via EMG time-frequency analysis at the paravertebral L5, L2, T10, and vastus lateralis (VL) electrode sites. Two parameters for assessing fatigue during dynamic contractions [i.e., the Instantaneous Median Frequency (IMDF) and its time dependent change] were shown to be reproducible both in the short-term (2 h) and long-term (2 wk). The corresponding ICCs reflecting the reproducibility of values between sessions were 96.9% (L5), 98.1% (L2), 90.1% (T10), 96.4% (UT), 98.0% (GM), 89.5% (VL), and 99.0% (BF), respectively. For most EMG recording sites, the reliability of the IMDF measures was not dependent upon the postural strategy that the subject used to accomplish the lifting task or on the subject's strength as measured via the static maximum lifting test. A comparison between the ICC values of the IMDF measures and those of the parameters utilized to assess fatigue during static sustained lifts [i.e., the Median Frequency (MDF) and its change during the test] revealed equally good reproducibility for most EMG recording sites. The respective ICC values that took into account time dependent trends for the IMDF parameter were 87.1% (L5), 62.4% (L2), 90.1% (T10), 0% (UT), 72.7% (GM), 45.4% (VL), and 100% (BF), and for the MDF parameter 94.9% (L5), 73.0% (L2), 80.9% (T10), 100% (UT), 89% (GM), 91.7% (VL), and 90.9% (BF), respectively. CONCLUSIONS: The time-frequency approach allows one to derive EMG spectral parameters that can be used to monitor muscle fatigue during dynamic real-world tasks such as lifting.