Search for Lepton Number and Flavor Violation in K

Searches for the lepton number violating K^{+}→π^{-}µ^{+}e^{+} decay and the lepton flavor violating K^{+}→π^{+}µ^{-}e^{+} and π^{0}→µ^{-}e^{+} decays are reported using data collected by the NA62 experiment at CERN in 2017-2018. No evidence for these decays is found and upper limits of the branching ratios are obtained at 90% confidence level: B(K^{+}→π^{-}µ^{+}e^{+})<4.2×10^{-11}, B(K^{+}→π^{+}µ^{-}e^{+})<6.6×10^{-11} and B(π^{0}→µ^{-}e^{+})<3.2×10^{-10}. These results improve by 1 order of magnitude over previous results for these decay modes.

Intravenous immunoglobulin as an adjunct therapy in persisting heparin-induced thrombocytopenia.

Heparin induced thrombocytopenia (HIT) is a serious adverse drug reaction caused by transient antibodies against platelet factor 4 (PF4)/heparin complexes, resulting in platelet activation and potentially fatal arterial and/or venous thrombosis. Most cases of HIT respond to cessation of heparin and administration of an alternative non-heparin anticoagulant, but there are cases of persisting HIT, defined as thrombocytopenia due to platelet activation/consumption for greater than seven days despite standard therapy. These patients remain at high risk for thrombotic events, which may result in limb-loss and mortality. Intravenous immunoglobulin (IVIg) has been proposed as an adjunct therapy for these refractory cases based on its ability to saturate FcγRIIa receptors on platelets, thus preventing HIT antibody binding and platelet activation. We describe 2 cases of persisting HIT (strongly positive antigen and functional assays, and persisting thrombocytopenia >7 days) with rapid clinical response to IVIg. We performed in-vitro experiments to support IVIg response. Healthy donor platelets (1 × 10e6) were treated with PF4 (3.75 µg/mL) for 20 min followed by 1-hour incubation with patients' sera. Platelet activation with and without addition of IVIg (levels equivalent to those reached in a patient after treatment with 2 gm/Kg) was evaluated in the PF4-dependent P-selectin expression assay (PEA). A significantly decreased platelet activation was demonstrated after the addition of IVIg to both patient samples, which correlated well with the rapid clinical response that each patient experienced. Thus, our study supports the use of IVIg as an adjunct therapy for persisting HIT.

Developing a multidisciplinary Young Women's Blood Disorders Program: a single-centre approach with guidance for other centres.

INTRODUCTION: Bleeding from the reproductive tract in women is a natural event, generally occurring with menstruation and childbirth. Women with an underlying bleeding disorder may experience heavy menstrual bleeding (HMB) and thereby, unacceptable blood loss. Up to 20% of US women with abnormal uterine bleeding and a normal gynaecological exam may have an underlying bleeding disorder corresponding to almost 2-3 million American women. These females face many obstacles in achieving optimum medical care for their problems. A haematologist may not evaluate these women as they are treated symptomatically. Recognition of an underlying bleeding disorder is not straightforward and many come to attention after serious bleeding events. Although mortality from HMB is uncommon, the true burden of HMB is its impact on health-related quality of life. To address these issues, women with HMB require a comprehensive approach to their care. METHODS: These reasons compelled us to institute a multidisciplinary Young Women's Blood Disorders (YWBD) Program at our institution. RESULTS: Herein, we describe the process of developing this program involving paediatric haematology, adolescent medicine and paediatric/adolescent gynaecology, and the expertise of a laboratory coagulationist, a nutritionist and nursing professionals. We also describe our experience with patient selection, the role of each specialty in the program, our approach to testing, the coordination of care and overall management of this patient population. Lastly, we propose metrics that could be followed in justifying the support of such a program. CONCLUSIONS: There is a growing need to offer comprehensive care to women with HMB and blood disorders. The YWBD program at our institution appears to be successful in delivering optimal care to young women affected with HMB.

New upper limit on strange quark matter abundance in cosmic rays with the PAMELA space experiment.

In this work we present results of a direct search for strange quark matter (SQM) in cosmic rays with the PAMELA space spectrometer. If this state of matter exists it may be present in cosmic rays as particles, called strangelets, having a high density and an anomalously high mass-to-charge (A/Z) ratio. A direct search in space is complementary to those from ground-based spectrometers. Furthermore, it has the advantage of being potentially capable of directly identifying these particles, without any assumption on their interaction model with Earth's atmosphere and the long-term stability in terrestrial and lunar rocks. In the rigidity range from 1.0 to ∼1.0×10^{3} GV, no such particles were found in the data collected by PAMELA between 2006 and 2009. An upper limit on the strangelet flux in cosmic rays was therefore set for particles with charge 1≤Z≤8 and mass 4≤A≤1.2×10^{5}. This limit as a function of mass and as a function of magnetic rigidity allows us to constrain models of SQM production and propagation in the Galaxy.

Cosmic-ray positron energy spectrum measured by PAMELA.

Precision measurements of the positron component in the cosmic radiation provide important information about the propagation of cosmic rays and the nature of particle sources in our Galaxy. The satellite-borne experiment PAMELA has been used to make a new measurement of the cosmic-ray positron flux and fraction that extends previously published measurements up to 300 GeV in kinetic energy. The combined measurements of the cosmic-ray positron energy spectrum and fraction provide a unique tool to constrain interpretation models. During the recent solar minimum activity period from July 2006 to December 2009, approximately 24,500 positrons were observed. The results cannot be easily reconciled with purely secondary production, and additional sources of either astrophysical or exotic origin may be required.

Cosmic-ray electron flux measured by the PAMELA experiment between 1 and 625 GeV.

Precision measurements of the electron component in the cosmic radiation provide important information about the origin and propagation of cosmic rays in the Galaxy. Here we present new results regarding negatively charged electrons between 1 and 625 GeV performed by the satellite-borne experiment PAMELA. This is the first time that cosmic-ray e⁻ have been identified above 50 GeV. The electron spectrum can be described with a single power-law energy dependence with spectral index -3.18 ± 0.05 above the energy region influenced by the solar wind (> 30 GeV). No significant spectral features are observed and the data can be interpreted in terms of conventional diffusive propagation models. However, the data are also consistent with models including new cosmic-ray sources that could explain the rise in the positron fraction.

PAMELA measurements of cosmic-ray proton and helium spectra.

Protons and helium nuclei are the most abundant components of the cosmic radiation. Precise measurements of their fluxes are needed to understand the acceleration and subsequent propagation of cosmic rays in our Galaxy. We report precision measurements of the proton and helium spectra in the rigidity range 1 gigavolt to 1.2 teravolts performed by the satellite-borne experiment PAMELA (payload for antimatter matter exploration and light-nuclei astrophysics). We find that the spectral shapes of these two species are different and cannot be described well by a single power law. These data challenge the current paradigm of cosmic-ray acceleration in supernova remnants followed by diffusive propagation in the Galaxy. More complex processes of acceleration and propagation of cosmic rays are required to explain the spectral structures observed in our data.

PAMELA results on the cosmic-ray antiproton flux from 60 MeV to 180 GeV in kinetic energy.

The satellite-borne experiment PAMELA has been used to make a new measurement of the cosmic-ray antiproton flux and the antiproton-to-proton flux ratio which extends previously published measurements down to 60 MeV and up to 180 GeV in kinetic energy. During 850 days of data acquisition approximately 1500 antiprotons were observed. The measurements are consistent with purely secondary production of antiprotons in the Galaxy. More precise secondary production models are required for a complete interpretation of the results.

An anomalous positron abundance in cosmic rays with energies 1.5-100 GeV.

Antiparticles account for a small fraction of cosmic rays and are known to be produced in interactions between cosmic-ray nuclei and atoms in the interstellar medium, which is referred to as a 'secondary source'. Positrons might also originate in objects such as pulsars and microquasars or through dark matter annihilation, which would be 'primary sources'. Previous statistically limited measurements of the ratio of positron and electron fluxes have been interpreted as evidence for a primary source for the positrons, as has an increase in the total electron+positron flux at energies between 300 and 600 GeV (ref. 8). Here we report a measurement of the positron fraction in the energy range 1.5-100 GeV. We find that the positron fraction increases sharply over much of that range, in a way that appears to be completely inconsistent with secondary sources. We therefore conclude that a primary source, be it an astrophysical object or dark matter annihilation, is necessary.

One-day surgery for acquired forefoot deformity: sciatic nerve blockade with mepivacaine vs mepivacaine+ropivacaine: a prospective, randomized study.

AIM: The aim of the study was to determine the doses of ropivacaine combined with mepivacaine for sciatic nerve blockade to enable the extension of analgesia without prolonged motor blockade, for the management of very painful operations in one-day surgery. METHODS: After obtaining approval by the ethics committee and written informed consent, we recruited 30 ASA I-III patients undergoing corrective orthopedic surgery of the forefoot in one-day surgery with sciatic nerve blockade. The patients were randomly divided into 3 groups: one control group, treated by 1.5% mepivacaine (300 mg), and two groups differentiated by the dose of 0.5% ropivacaine (25 and 40 mg) used in combination with 1.5% mepivacaine (225 mg). The offset data of the blockade were obtained by a self-assessment form filled in by the patients, and a direct check on discharge by a blinded observer. RESULTS: There was no significant difference in the duration of the blockade among the 3 groups; the extension of analgesia was significant (P<0.003) in the group treated by mepivacaine+ropivacaine 40 mg (mean 477+/-255 min). CONCLUSION: Adequate doses of ropivacaine added to mepivacaine for peripheral blockade produce and increase the duration of analgesia without influencing the criteria for discharge after Day Surgery.

Pacemaker-induced mitral regurgitation: prominent role of abnormal ventricular activation sequence versus altered atrioventricular synchrony.

BACKGROUND: Functional mitral regurgitation is a hemodynamic adverse consequence of right ventricular apical pacing that profoundly modifies the contraction and relaxation of the left ventricle by inverting and delaying its activation sequence. The aim of this study was to analyze by Doppler echocardiography in the acute setting the true incidence and the mechanism responsible for the right ventricular apical pacing-induced mitral regurgitation. METHODS: We studied 27 consecutive patients submitted to pacemaker implantation (VVI n = 9; DDD n = 18) because of bradyarrhythmias. The exclusion criteria were structural cardiac disease and permanent atrioventricular block. Patients underwent Doppler echocardiographic examination during both spontaneous rhythm (pacemaker off) as well as during programmed pacing at a rate of 70 b/min. In case of a double chamber pacemaker, a non-optimized atrioventricular delay of 150 ms was chosen. RESULTS: Two groups were identified: 11 patients with (Group 1, mean age 71 +/- 7 years) and 16 patients without (Group 2, mean age 71 +/- 4 years) new-onset pacing-induced mitral regurgitation. The incidence of mitral regurgitation was found to be higher during DDD (33%) than during VVI (24%) pacing mode. The relationship between gender and the occurrence of pacing-induced mitral regurgitation was striking: 10/13 women (77%) presented with mitral regurgitation during acute right ventricular apical pacing while this complication occurred in only 1/14 men (7%). Moreover, analysis of variance (ANOVA) and post-hoc pairwise multiple comparison showed an increased size of the mitral apparatus, as defined by the enlargement of the annulus (long axis 28 +/- 3 vs 23 +/- 2 mm; short axis 25 +/- 3 vs 20 +/- 3 mm, p = 0.05) and the lengthening of the anterior mitral leaflet (23 +/- 4 vs 18 +/- 2 mm, p = 0.05) and chordae tendineae (16 +/- 3 vs 13 +/- 2 mm, p = 0.05). This was probably related to the high female prevalence (91%) in Group 1 as compared to the control group (50 healthy subjects; 17 men, 33 women; mean age 71 +/- 8 years). No significant differences were observed between Group 2 and controls. CONCLUSIONS: Our study confirmed that functional mitral regurgitation is a frequent consequence of right ventricular apical pacing. Despite the maintenance of normal atrioventricular synchrony, we found that the pathway for ventricular depolarization was the critical determinant of normal mitral valve function. Such data show the importance of the preservation of a normal ventricular activation sequence during permanent cardiac pacing where it is technically feasible. Female patients seemed to be exposed to a higher risk of pacing-induced mitral regurgitation due to an anatomic predisposing condition of the mitral apparatus and to the left ventricular dyssynchronous contraction secondary to right ventricular apical pacing.

Repolarization changes in a double-blind crossover study of dofetilide versus sotalol in the treatment of ventricular tachycardia.

UNLABELLED: The aim of this study was to determine whether a therapeutic response to Class III antiarrhythmic drugs is related to predictable changes in repolarization on the electrocardiogram (ECG). A group of 57 patients with ischemic heart disease and inducible ventricular tachycardia (VT) at electrophysiological study (EPS) were selected from a population enrolled in a randomized double-blind crossover study of dofetilide (500 micrograms bid) versus sotalol (160 mg bid). ECGs were analyzed blindly, and RR, QT (maximum value/12 leads), QTc (Bazett's formula), QT dispersion (QTmax-QTmin over 12 leads) and QTc dispersion, were calculated at baseline and on the third day of treatment (4 hours after dosing), when patients underwent EPS to test the effects of study drugs on VT inducibility. RESULTS: At EPS 21 patients were responders to dofetilide and 22 to sotalol. On day 3, a significant increase in QT and QTc and decrease in QT and QTc dispersion, compared to baseline, was measured in responders and nonresponders, with both dofetilide and sotalol. No significant difference in QTc or QT dispersion between responders and nonresponders was observed in either treatment group. In conclusion, treatment with dofetilide and sotalol was associated with an increase in QT and QTc, and a decrease in QT and QTc dispersion. In contrast with previous reports, a differential effect on QT or QTc dispersion was not observed in drug responders versus nonresponders.

Isolation of HTLV-1 from an aggressive form of ATL in a Romanian patient not at risk of infection and with seronegative family members.

We present the clinical, virological and haematochemical data of a 22 year old patient from Romania with Adult T Cell Leukaemia (ATL). Viral isolation in peripheral mononuclear blood cells (PMBC), detection of DNA sequences of HTLV-1 by Polymerase Chain Reaction (PCR) and of antibodies by Elisa and Western blot were performed. The patient does not belong to any risk group and additionally all members of her family are seronegative for HTLV-1, the aetiological agent of ATL. The role of viral infection remains open.

Autotransfusion in major orthopaedic surgery: experience with 1785 patients.

Using a prospective audit, we have evaluated the efficacy of an integrated autotransfusion regimen which comprised predepositing and intra- and postoperative blood salvage in major orthopaedic surgery. We examined prospectively the records of 1785 patients (1198 females, 5867 males, mean age 62 (range 16-90) yr, preoperative haemoglobin concentration 13.4 (SD 1.4) g dl-1) undergoing total hip arthroplasty (THA, 1229 patients), THA after removal of internal fixation devices (RFD + THA, 18 patients), total knee arthroplasty (TKA, 263 patients), revision surgery of the hip (HR cup + stem revision, 197 patients; cup revision, 53 patients; stem revision, 16 patients) and total knee revision (TKR, nine patients). We estimated that the number of predonations (MSBOS = maximum surgery blood order schedule) was 2 u. for THA, TKA and TKR, and 3 u. for partial or total hip revision and total hip arthroplasty with fixation removal. We found that it was possible to obtain the MSBOS in 1597 patients (89.5%). Homologous red blood cell (HRBC) transfusions were carried out in 131 patients (7.3%). We found that the need to use HRBC was significantly associated with failure to meet the number of MSBOS, female sex, lower preoperative haemoglobin concentration, use of calcium heparin for antithrombosis prophylaxis, more extensive surgery, higher ASA rating and co-existing diseases such as coronary artery disease.

[Carotid thromboendarterectomy: personal experience and review of the literature]. / Tromboendoarterectomia carotidea: esperienza personale ed analisi della letteratura.

Carotid endoarterectomy (CEA) is known to prevent cerebrovascular accidents. Between February 1987 and December 1993 we performed 97 CEA on 82 patients (62 male and 20 female, median age 66 +/- 7.6 years) 95.1% reported previous hemispheric neurological accidents; 4.9% were asymptomatic. Operative indications for asymptomatic patients were high degree stenosis (> 70%) of the internal carotid artery and ulcerated plaques with a moderate degree (50%) of stenosis. Major events (transient ischemic attack and stroke) were recorded in 73.2% cases. Preoperative investigations consisted of Duplex scan, arteriography, and cerebral CT scan or NMR. Operative mortality was 2.06% (2 cases) and perioperative stroke was 5.1% (5 cases). The sensibility, sensitivity and accuracy of Duplex scan to detect ulcerated plaques was 88.7%, 85.2% and 87.5% respectively. At a median follow-up of 33 months (range 6-81 months) 74 (92.5%) patients are free of strokes whereas 1 patient died for stroke. In our series the annual incidence of stroke was 0.5%. Our results suggest that Duplex scan is a reliable exam to investigate the carotid axis and CEA is a safe operation that prevents future cerebrovascular accidents.

Methods of blood saving in revision surgery of the hip.

The blood saving protocol, which is the product of 15 years of experience, has gradually been improved, until the current form has been achieved, which includes predeposit, acute intentional isovolemic hemodilution, controlled hypotension, intraoperative blood recovery, postoperative monitoring and blood recovery, external compressive elastic dressing. The acceptance of values for hemoglobin which may even be < 8 g/dl during the late postoperative period, as long as this is well-tolerated by patients, has allowed us to drastically reduce the use of homologous transfusions. Over the last 2 years, out of 59 autotransfused patients submitted to revision surgery of the hip, only 9 (equal to 15%) required homologous transfusion. An analysis of the data shows that the use of homologous blood is associated with the presence of ischemic cardiopathy (p < 0.001) and with a predeposit which is less than 4 units of blood (packed red blood cell+fresh frozen plasma) (p = 0.05).

Autotransfusion: 15 years experience at Rizzoli Orthopaedic Institute.

The program of blood saving, result of 15 years of experience, includes predeposit (1977) hemodilution (1979) intra (1984) and postoperative (1985) salvage, careful intra and postoperative bleeding control, use of homologous transfusion only in case of intolerated anaemia even for 7-8g/dl Hb values. The use of autologous compared to homologous transfusion passed from 19% in 1984 to 62% in 1992. In 1992 in the surgical division of the 1st Anaesthesia and Intensive Care unit, 414 patients underwent prosthetic hip and knee surgery, 8% of these patients were homologously transfused.