Salmeterol and formoterol in partially reversible severe chronic obstructive pulmonary disease: a dose-response study

AbstractWhen testing the response to β2-agonist drugs in severe chronic obstructive pulmonary disease (COPD), a dose-response assessment should be undertaken. This study compares the time course of inhaled salmeterol (25, 50 and 75 μg) and formoterol (12, 24 and 36 μg) at different doses in a group of 12 patients with partially reversible, but severe COPD (FEV1 of 12–32% of predicted values after β2-agonist drugs had been withheld for 24 h). All doses of salmeterol and formoterol induced a significant (P<0·01) spirometric improvement over the 12-h monitoring period, when compared to the spirometric improvement after placebo, but while formoterol induced a dose-dependent increase of the FVC, FEV1 and FEF50, this was not the case for salmeterol. In fact, 75 μg salmeterol did not produce a further improvement of these parameters. Mean peak bronchodilation, expressed as the increase in FEV1 over baseline values, occurred 2 h after inhalation of the three doses of salmeterol, and 1 h after inhalation of the three doses of formoterol. A comparison of 50 μg salmeterol with 12 μg or 24 μg formoterol (clinically recommended doses), showed that improvement of FEV1 after salmeterol was statistically (P<0·05) higher than that after the two doses of formoterol, although the mean peak bronchodilations were similar. This was because salmeterol has a longer duration of action than formoterol. These data demonstrate that salmeterol is equally effective as, but longer-acting than, formoterol at clinically recommended doses in patients suffering from COPD, with severe airway obstruction. Moreover, these data suggest that 50 μg is the best dosage for salmeterol in these patients

Ultimate limits for quantum magnetometry via time-continuous measurements

We address the estimation of the magnetic field B acting on an ensemble of atoms with total spin J subjected to collective transverse noise. By preparing an initial spin coherent state, for any measurement performed after the evolution, the mean-square error of the estimate is known to scale as , i.e. no quantum enhancement is obtained. Here, we consider the possibility of continuously monitoring the atomic environment, and conclusively show that strategies based on time-continuous non-demolition measurements followed by a final strong measurement may achieve Heisenberg-limited scaling and also a monitoring-enhanced scaling in terms of the interrogation time. We also find that time-continuous schemes are robust against detection losses, as we prove that the quantum enhancement can be recovered also for finite measurement efficiency. Finally, we analytically prove the optimality of our strategy

Tetraquarks and Pentaquarks in String Models

We consider the production and decay of multiquark systems in the framework of string models where the hadron structure is determined by valence quarks together with string junctions. We show that the low mass multiquark resonances can be very narrow.Comment: 7 pages, 2 figure

Frameless stereotactic biopsy for precision neurosurgery : diagnostic value, safety, and accuracy

BACKGROUND: Stereotactic biopsy is consistently employed to characterize cerebral lesions in patients who are not suitable for microsurgical resection. In the past years, technical improvement and neuroimaging advancements contributed to increase the diagnostic yield, the safety, and the application of this procedure. Currently, in addition to histological diagnosis, the molecular analysis is considered essential in the diagnostic process to properly select therapeutic and prognostic algorithms in a personalized approach. The present study reports our experience with frameless stereotactic brain biopsy in this molecular era. METHODS: One hundred forty consecutive patients treated from January 2013 to September 2018 were analyzed. Biopsies were performed using the Brainlab Varioguide\uae frameless stereotactic system. Patients' clinical and demographic data, the time of occupation of the operating room, the surgical time, the morbidity, and the diagnostic yield in providing a histological and molecular diagnosis were recorded and evaluated. RESULTS: The overall diagnostic yield was 93.6% with nine procedures resulting non-diagnostic. Among 110 patients with glioma, the IDH-1 mutational status was characterized in 108 cases (98.2%), resulting wild-type in all subjects but 3; MGMT methylation was characterized in 96 cases (87.3%), resulting present in 60 patients, and 1p/19q codeletion was founded in 6 of the 20 cases of grade II-III gliomas analyzed. All the specimens were apt for molecular analysis when performed. Bleeding requiring surgical drainage occurred in 2.1% of the cases; 8 (5.7%) asymptomatic hemorrhages requiring no treatment were observed. No biopsy-related mortality was recorded. Median length of hospital stay was 5 days (IQR 4-8) with mean surgical time of 60.77 min (\ub1\u200923.12) and 137.44\u2009\ub1\u200924.1 min of total occupation time of the operative room. CONCLUSIONS: Stereotactic frameless biopsy is a safe, feasible, and fast procedure to obtain a histological and molecular diagnosis

2021 international consensus statement on optical coherence tomography for basal cell carcinoma: image characteristics, terminology and educational needs

Background Despite the widespread use of optical coherence tomography (OCT) for imaging of keratinocyte carcinoma, we lack an expert consensus on the characteristic OCT features of basal cell carcinoma (BCC), an internationally vetted set of OCT terms to describe various BCC subtypes, and an educational needs assessment. Objectives To identify relevant BCC features in OCT images, propose terminology based on inputs from an expert panel and identify content for a BCC-specific curriculum for OCT trainees. Methods Over three rounds, we conducted a Delphi consensus study on BCC features and terminology between March and September 2020. In the first round, experts were asked to propose BCC subtypes discriminable by OCT, provide OCT image features for each proposed BCC subtypes and suggest content for a BCC-specific OCT training curriculum. If agreement on a BCC-OCT feature exceeded 67%, the feature was accepted and included in a final review. In the second round, experts had to re-evaluate features with less than 67% agreement and rank the ten most relevant BCC OCT image features for superficial BCC, nodular BCC and infiltrative and morpheaphorm BCC subtypes. In the final round, experts received the OCT-BCC consensus list for a final review, comments and confirmation. Results The Delphi included six key opinion leaders and 22 experts. Consensus was found on terminology for three OCT BCC image features: (i) hyporeflective areas, (ii) hyperreflective areas and (iii) ovoid structures. Further, the participants ranked the ten most relevant image features for nodular, superficial, infiltrative and morpheaform BCC. The target group and the key components for a curriculum for OCT imaging of BCC have been defined. Conclusion We have established a set of OCT image features for BCC and preferred terminology. A comprehensive curriculum based on the expert suggestions will help implement OCT imaging of BCC in clinical and research settings

Pattern of statin use in southern Italian primary care: Can prescription databases be used for monitoring long-term adherence to the treatment?

Objectives: We sought to evaluate the prescribing pattern of statins according to national and regional health policy interventions and to assess specifically the adherence to the therapy in outpatient setting in Southern Italy. Methods: A population-based study was performed on persons ≥15 years old, living in the catchment area of Caserta (Southern Italy), and registered in Arianna database between 2004 and 2010. Prevalence and incidence of new treatments with statins were calculated for each year and stratified by drug. Adherence to therapy was measured by Medication Possession Ratio. Sub-analyses by individual compound and type of cardiovascular prevention were performed. Results: From 2004 to 2010, the one-year prevalence of statin use increased from 44.9/1,000 inhabitants to 79.8/1,000, respectively, consistently with the incidence of new use from 16.2/1,000 to 19.5/1,000, except a slight decrease after criteria reimbursement revision

Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis.

The presence of the endogenous &lt;i&gt;Leishmania&lt;/i&gt; RNA virus 1 (LRV1) replicating stably within some parasite species has been associated with the development of more severe forms of leishmaniasis and relapses after drug treatment in humans. Here, we show that the disease-exacerbatory role of LRV1 relies on type I IFN (type I IFNs) production by macrophages and signaling in vivo. Moreover, infecting mice with the LRV1-cured &lt;i&gt;Leishmania guyanensis&lt;/i&gt; ( &lt;i&gt;LgyLRV1&lt;/i&gt; &lt;sup&gt; &lt;i&gt;-&lt;/i&gt; &lt;/sup&gt; ) strain of parasites followed by type I IFN treatment increased lesion size and parasite burden, quantitatively reproducing the LRV1-bearing ( &lt;i&gt;LgyLRV1&lt;/i&gt; &lt;sup&gt; &lt;i&gt;+&lt;/i&gt; &lt;/sup&gt; ) infection phenotype. This finding suggested the possibility that exogenous viral infections could likewise increase pathogenicity, which was tested by coinfecting mice with &lt;i&gt;L. guyanensis&lt;/i&gt; and lymphocytic choriomeningitis virus (LCMV), or the sand fly-transmitted arbovirus Toscana virus (TOSV). The type I IFN antiviral response increased the pathology of &lt;i&gt;L. guyanensis&lt;/i&gt; infection, accompanied by down-regulation of the IFN-γ receptor normally required for antileishmanial control. Further, LCMV coinfection of IFN-γ-deficient mice promoted parasite dissemination to secondary sites, reproducing the &lt;i&gt;LgyLRV1&lt;/i&gt; &lt;sup&gt; &lt;i&gt;+&lt;/i&gt; &lt;/sup&gt; metastatic phenotype. Remarkably, LCMV coinfection of mice that had healed from &lt;i&gt;L. guyanensis&lt;/i&gt; infection induced reactivation of disease pathology, overriding the protective adaptive immune response. Our findings establish that type I IFN-dependent responses, arising from endogenous viral elements (dsRNA/LRV1), or exogenous coinfection with IFN-inducing viruses, are able to synergize with New World &lt;i&gt;Leishmania&lt;/i&gt; parasites in both primary and relapse infections. Thus, viral infections likely represent a significant risk factor along with parasite and host factors, thereby contributing to the pathological spectrum of human leishmaniasis