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The primary aim of this study was to describe the use of primary anti-infective prophylaxis (AP) in common clinical practice in patients affected by immune thrombocytopenia (ITP) and treated with RTX. Population studied consisted of patients affected by ITP (age ≥ 18 years) who had received at least one dose of RTX from January 2008 to June 2018. Five Italian haematology centres participated in the current study. Data were retrospectively collected: demographic data (age, gender), concomitant comorbidities and previous therapies for ITP, characteristics of AP, the occurrence of infections and their management. The ITP cohort consisted of 67 patients sub-grouped into two categories according to the administration of AP: (1) treated with AP (N= 34; 51%) and (2) not treated with AP (N=33, 49%). AP consisted of combined trimethoprim/sulfamethoxazole (TMP/SMX) and acyclovir (AC) in half of patients. TPM/SMX as a single agent was adopted in 32% patients and one patient received only AC. Overall, infections were experienced in 15% of patients during follow-up with a similar proportion in the 2 groups (treated and not treated) of patients (14.7% vs 15%). Clinical course of infections was however, less severe in patients treated with AP, where all infections were grade 2 and did not require hospitalization. In neither group of patients was reported Pneumocystis pneumonia. In conclusion, despite the absence of clear evidence, our analysis shows that AP in patients with ITP receiving RTX is frequently adopted, even if in the absence of well-defined criteria. Prophylaxis administration is quite consistent within the same haematological Center; thus, it seems related to clinicians' experience.

We enumerate and characterize some classes of alternating and reverse alternating involutions avoiding a single pattern of length three or four. If on one hand the case of patterns of length three is trivial, on the other hand, the length four case is more challenging and involves sequences of combinatorial interest, such as Motzkin and Fibonacci numbers.

We enumerate involutions avoiding any single pattern of length three according to the statistic ‘number of visible pairs’, namely, the number of non-adjacent columns in the bargraph representation ...

Over the last few years, we assisted to an increasing knowledge about acute myeloid leukemia (AML) pathobiology. However, outcomes remain unsatisfactory particularly for adult patients over 60 years old. Not surprisingly several cases of therapy-related AML (tAML) and secondary AML, both characterized by poorer prognosis, are more common in older population. For several decades initial therapy for AML remained unchanged and typically treatment consisted of an anthracycline combined with continuous infusion of cytarabine for 7 days, the so-called "7+3" standard regimen. The efforts made by the researchers to improve this standard schedule, have led to only modest improvement in the response rate (RR) but no change in overall survival (OS), until the recent evolution seen with new target specific mutation therapies. In 2017, a new liposomal-encapsulated formulation with daunorubicin and cytarabine (CPX-351) was approved by the US Food and Drug Administration for the treatment of newly diagnosed tAML or AML with myelodysplasia-related changes (AML-MRCs). Based on the findings that ratiometric delivery may be more effective than administration of either drug at their maximum tolerated dose (MTD), CPX-351 was designed to deliver a fixed 5:1 molar ratio of the two molecules historically used in the standard "7+3" regimen, cytarabine and daunorubicin respectively. CPX-351 did show improvements of overall survival compared to traditional "7+3" in newly diagnosed secondary and therapy-related AML in adult patients. However, questions remain regarding how to select across AML patient subgroups to maximize the clinical benefit. Possible future directions include evaluating CPX-351 dose intensification, combining this liposomal formulation with targeted therapies and not least important a better understanding about the mechanism of improved responses in tAML and AML-MRC, two entities recognized to be less chemo-sensitive than other hematologic malignancies. In summary, CPX-351 offers finally something new in the landscape of AML therapy. Herein we will review the rationale behind this new drug product development, the main pharmacological characteristics, and discuss the results of clinical trials that led to its FDA approval at first and by EMA in 2018.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy, characterized by poor prognosis if treated with conventional therapy. Allogenic hematologic stem cell transplant can improve survival and can be curative, but it is available in a small percentage of patients given that the median age at diagnosis is 70 years. In this scenario it is assumed that only the development of precision medicine-driven therapy will change BPDCN patient prognosis. CD123 (the α-subunit of interleukin (IL)-3 receptor) is over-expressed on BPDCN cells surface and seems to be the ideal marker to develop antibody-based therapies. Tagraxofusp (Elzonris®), a recombinant immunotoxin consisting of human interleukin-3 fused to a truncated diphtheria toxin, has been approved by FDA in December 2018 for the treatment of BPDCN in adult and pediatric patients. tagraxofusp has shown promising clinical activity, with a high overall response rate and quite manageable safety profile even in elderly patients. It seems to improve overall survival too, but comparative trials are necessary to confirm this. Adverse events are commonly reported and the most important are transaminitis, thrombocytopenia and capillary leak syndrome (CLS). Therefore, to prevent the onset of severe CLS is recommended to reserve tagraxofusp for patients with preserved hepatic and cardiac functions, and to strictly observe serum albumin level. Further studies are required to resolve many several unanswered questions about tagraxofusp. In this review, we will resume and discuss pharmacological characteristic of tagraxofusp, results of clinical trials leading to its approval by FDA in 2018 and future perspectives about its use in BPDCN and other hematological malignancies.

Supplemental material, sj-pdf-1-opp-10.1177_1078155220918025 for Stability of calcium levofolinate reconstituted in syringes and diluted in NaCl 0.9% and glucose 5% polyolefin/polyamide infusion bags by Seydou Sanogo, Paolo Silimbani, Raffaella Gaggeri and Carla Masini in Journal of Oncology Pharmacy Practice

Supplemental material, sj-pdf-2-opp-10.1177_1078155220918025 for Stability of calcium levofolinate reconstituted in syringes and diluted in NaCl 0.9% and glucose 5% polyolefin/polyamide infusion bags by Seydou Sanogo, Paolo Silimbani, Raffaella Gaggeri and Carla Masini in Journal of Oncology Pharmacy Practice

Background The aseptic preparation of oncologic drugs is performed in the centralised, pharmacy-based cytotoxic drugs preparation unit equipped with a biological safety cabinet and the robotic system APOTECAchemo (Loccioni, Italy), installed in 2012. Manual and fully automated preparations run in parallel are operated by two and one pharmacy technicians (PT), respectively. On average, the annual workload amounts to 35 000 preparations, two-thirds of which are prepared with the robotic system. Purpose The aim of this study was to evaluate the working efficiency of PT after implementing the robotic system and calculate the amount of preparations to be transferred from the manual to the automated process to optimize human resources’ utilisation. Material and methods Manual and automated preparation were analysed over three years (2014–2016). Full-time equivalents (FTE) required by both processes were calculated for each year. A FTE of 1.0 was equivalent to a PT working full-time 40 hours per week, 1,700 hours per year. The throughput in terms of annual preparations per FTE was calculated including direct activities (compounding) and indirect activities related to production (quality controls and standard operating procedures, e.g. cleaning and gowning). The calculation was performed for both manual and automated preparation processes. Results On average, the overall working time spent by PT on direct and indirect activities amounted to 4,670 hours/year for the manual process and to 2,441 hours/year for the automated process, resulting in 14 151 and 21 534 preparations, respectively. The annual amount of preparations per 1.0 FTE in the automated process (mean: 15,066) was three times higher than in the manual process (mean: 5,036). The production times were comparable, but the working time spent by PT on indirect activities was reduced by 85% by using the robotic system. Each 7600 preparation transferred from the manual process to the robotic system results in 1.0 FTE made available for different working activities. Conclusion Results of this study revealed that the automated process with the robotic system improves the working efficiency of PT, thereby allowing the reallocation of human resources and the optimisation of workload distribution in the daily pharmacy practice. Other indirect advantages related to cost and production quality are achieved. References and/or acknowledgements No conflict of interest.

The knowledge of the chemical stability of drugs prepared and administered in hospital is of paramount importance for establishing the methods and times of their preparation, as well as for ensuring patient safety. The objective of this work was to develop and validate a single chromatographic method, according to the International Conference on Harmonization (ICH), United States Pharmacopeia (USP) and the European Pharmacopoeia (Ph. Eur.) guidelines, to allow the determination of the chemical stability of 5 chemotherapy drugs. The high performance liquid chromatography coupled with diode array detection (HPLC-DAD) method developed was found to be linear (all analytical curves showed R2 ≥ 0.999), sensitive, precise (RSDs

We define a map v between the symmetric group Sn and the set of pairs of Dyck paths of semilength n. We show that the map v is injective when restricted to the set of 1234-avoiding permutations and characterize the image of this map.

Centrosymmetric involutions in the symmetric group ${\mathcal S}_{2n}$ are permutations $\pi$ such that $\pi=\pi^{-1}$ and $\pi(i)+\pi(2n+1-i)=2n+1$ for all $i$ , and they are in bijection with involutions of the hyperoctahedral group. We describe the distribution of some natural descent statistics on $321$ -avoiding centrosymmetric involutions , including the number of descents in the first half of the involution, and the sum of the positions of these descents. Our results are based on two new bijections , one between centrosymmetric involutions in $ {\mathcal S} _{2n}$ and subsets of $\{1,\dots,n\}$ , and another one showing that certain statistics on Young diagrams that fit inside a rectangle are equidistributed . We also use the latter bijection to refine a known result stating that the distribution of the major index on $321$ -avoiding involutions is given by the $q$ -analogue of the central binomial coefficients.

// Alberto Farolfi 1 , Paolo Silimbani 2 , Davide Gallegati 3 , Elisabetta Petracci 4 , Alessio Schirone 1 , Mattia Altini 5 and Carla Masini 2 1 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 2 Oncology Pharmacy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 3 Financial and Management Control, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 4 Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 5 Healthcare Administration, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy Correspondence to: Alberto Farolfi, email: alberto.farolfi@irst.emr.it Keywords: breast cancer, economic evaluation, oncology, subcutaneous trastuzumab Received: February 07, 2017 Accepted: June 02, 2017 Published: June 16, 2017 ABSTRACT We conducted an economic evaluation of intravenous (IV) vs subcutaneous (SC) trastuzumab for the treatment of patients with early breast cancer (EBC). Data of patients receiving adjuvant IV trastuzumab at our institute in 2014 were used to study three different treatment scenarios: 1) IV trastuzumab, 2) SC trastuzumab, and 3) IV trastuzumab during chemotherapy followed by SC trastuzumab. Our cohort included 114 patients with a median weight of 63.75 kg. Scenario 2 was the most time-saving treatment, with 71.7% reduction in preparation time and 89.3% reduction in chair time compared to scenario 1. Considering full costs, the mean costs per patient/year were € 14,233 ± 8,698 for scenario 1, € 14,272 ± 8,312 for scenario 2, and € 14,535 ± 8,646 for scenario 3 ( p = 0.959). When mean body weight was > 65.2 kg, the mean cost was lower in scenario 2 than in scenario 1. Scenario 2 proved a valuable time-saving and cost-saving option. A shift from IV to SC trastuzumab should be considered, especially in capacity-constrained oncology departments.

We study the descent distribution over the set of centrosymmetric permutations that avoid the pattern of length 3. Our main tool in the most puzzling case, namely, $\tau=123$ and $n$ even, is a bijection that associates a Dyck prefix of length $2n$ to every centrosymmetric permutation in $S_{2n}$ that avoids 123., Comment: 17 pages, 6 figures

Combinatorics, We present an extensive study of the Eulerian distribution on the set of centrosymmetric involutions, namely, involutions in S(n) satisfying the property sigma(i) + sigma(n + 1 - i) = n + 1 for every i = 1 ... n. We find some combinatorial properties for the generating polynomial of such distribution, together with an explicit formula for its coefficients. Afterwards, we carry out an analogous study for the subset of centrosymmetric involutions without fixed points.

We show how a bijection due to Biane between involutions and labelled Motzkin paths yields bijections between Motzkin paths and two families of restricted involutions that are counted by Motzkin numbers, namely, involutions avoiding 4321 and 3412. As a consequence, we derive characterizations of Motzkin paths corresponding to involutions avoiding either 4321 or 3412 together with any pattern of length 3. Furthermore, we exploit the described bijection to study some notable subsets of the set of restricted involutions, namely, fixed point free and centrosymmetric restricted involutions., Comment: 22 pages, 10 figures

We introduce an infinite family of lower triangular matrices $\Gamma^{(s)}$, where $\gamma_{n,i}^s$ counts the standard Young tableaux on $n$ cells and with at most $s$ columns on a suitable subset of shapes. We show that the entries of these matrices satisfy a three-term row recurrence and we deduce recursive and asymptotic properties for the total number $\tau_s(n)$ of tableaux on $n$ cells and with at most $s$ columns., Comment: 11 pages, 1 figure

We establish a combinatorial connection between the sequence $(i_{n,k})$ counting the involutions on $n$ letters with $k$ descents and the sequence $(a_{n,k})$ enumerating the semistandard Young tableaux on $n$ cells with $k$ symbols. This allows us to show that the sequences $(i_{n,k})$ are not log-concave for some values of $n$, hence answering a conjecture due to F. Brenti., Comment: 10 pages

We define a map $\nu$ between the symmetric group $S_n$ and the set of pairs of Dyck paths of semilength $n$. We show that the map $\nu$ is injective when restricted to the set of 1234-avoiding permutations and characterize the image of this map., Comment: 16 pages, 8 figures

We exploit Krattenthaler's bijection between the set $S_n(3\textrm{-}1\textrm{-}2)$ of permutations in $S_n$ avoiding the classical pattern $3\textrm{-}1\textrm{-}2$ and Dyck $n$-paths to study the distribution of every consecutive pattern of length 3 on the set $S_n(3\textrm{-}1\textrm{-}2)$. We show that these consecutive patterns split into 3 equidistribution classes, by means of an involution on Dyck paths due to E.Deutsch. In addition, we state equidistribution theorems concerning triplets of statistics relative to the occurrences of the consecutive patterns of length 3 in a permutation., Comment: 18 pages, 7 figures

We present an extensive study of the Eulerian distribution on the set of self evacuated involutions, namely, involutions corresponding to standard Young tableaux that are fixed under the Sch$\ddot{\textrm{u}}$tzenberger map. We find some combinatorial properties for the generating polynomial of such distribution, together with an explicit formula for its coefficients. Afterwards, we carry out an analogous study for the subset of self evacuated involutions without fixed points., 18 pages

The experience of day surgery in 8 months of activity in our department is reported. Out of 95 cases of bladder tumour, 21 were selected according to certain specific and general characteristics and recommended for day surgery. Despite organisational difficulties, due to the distance between the place of operation and the ordinary in-patients ward and sometimes to patient dissatisfaction, from both an economic and organisational point of view we consider that the experience has not only been positive but should be increased.