Botulinum toxin type a as a therapeutic agent against headache and related disorders

Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A

When to start and when to stop antifibrotic therapies

Idiopathic pulmonary fibrosis (IPF) is characterised by progressive changes of the lung architecture causing cough and dyspnoea and ultimately leading to lung failure and death. Today, for the first time, two drugs that may reduce the inexorable progression of the disease are available, suggesting that treatment with specific drugs for IPF should be started as soon as diagnosis is made. This applies to any disease and particularly to IPF, which is marked by a 5-year survival comparable or even worse than many cancers. However, despite common sense and even worse, in spite of scientific data coming from clinical trials, post hoc analysis, long-term safety studies and real-life experiences, the question of when to start and when to stop treatment with antifibrotics is still debated. In IPF, particularly when the disease is diagnosed at an early stage, "wait and watch" behaviour is not rare to observe. This is largely due to the lack of awareness of both patients and clinicians regarding the progression of the disease and its prognosis. Another important issue is when treatment should be stopped. In general, there are two main reasons to stop a therapy: unbearable side-effects and/or lack of efficacy. According to current (although preliminary) evidence, antifibrotic drugs should not be discontinued except for safety issues

Pharmacologic pupil dilation as a predictive test for the risk for intraoperative floppy-iris syndrome

PURPOSE: To evaluate the effect of α1-adrenergic receptor antagonists (α1-ARAs) on pupil diameter and determine whether the diameter predicts intraoperative floppy-iris syndrome (IFIS). SETTING: Ophthalmology Section, Palermo University, Palermo, Italy. DESIGN: Prospective cohort study. METHODS: Male outpatients taking tamsulosin, α(1)-ARAs, or no α(1)-ARAs having phacoemulsification were recruited. Pupils were measured 1 month preoperatively, immediately preoperatively, and postoperatively under mesopic low (0.4 lux) and high (4.0 lux) illumination after pharmacologic dilation. The IFIS severity was graded. RESULTS: Each group comprised 50 patients. Pharmacologic dilation in both α(1)-ARA groups was statistically significantly less than in the no α1-ARA group 1 month preoperatively, immediately before surgery, and postoperatively (P=.001, P<.0005, and P<.0005, respectively). The IFIS incidence differed significantly between the tamsulosin and other α(1)-ARA groups and the no α1-ARA group (P<.0005 and P=.017, respectively) and between the tamsulosin group and the other α1-ARA group (P=.027). On regression analysis, the hazard ratio for overall IFIS incidence was 3.8 in the other α(1)-ARA group (P=.012) and 10.1 in the tamsulosin group (P<.0005). Pupil size was inversely related to IFIS incidence and severity (P<.0005). A dilated pupil of 7.0 mm or smaller had 73% sensitivity and 95% specificity for predicting IFIS (P=.0001). CONCLUSIONS: Pupil dilation was inhibited by α(1)-ARAs, in particular tamsulosin. For a pupil 7.0 mm or smaller, the risk for IFIS existed regardless of α(1)-ARAs treatment, which surgeons should take into consideration

Compliance to therapy with Dapoxetine in comparison to a conventional selective serotonin reuptake inhibitor (Citalopram) in 118 patients with premature ejaculation.

Premature Ejaculation (PE) is a sexual dysfunction that concern 20-30% of the male population. Dapoxetine is a new serotonine re-uptake inhibitor (SSRI)specific for PE treatment.Aim of the study is to assess compliance and effectiveness of the treatment with dapoxetine compared to the treatment with citalopram (a classic SSRI used to treat PE)

PLANT: A Method for Detecting Changes of Slope in Noisy Trajectories

Time traces obtained from a variety of biophysical experiments contain valuable information on underlying processes occurring at the molecular level. Accurate quantification of these data can help explain the details of the complex dynamics of biological systems. Here, we describe PLANT (Piecewise Linear Approximation of Noisy Trajectories), a segmentation algorithm that allows the reconstruction of time-trace data with constant noise as consecutive straight lines, from which changes of slopes and their respective durations can be extracted. We present a general description of the algorithm and perform extensive simulations to characterize its strengths and limitations, providing a rationale for the performance of the algorithm in the different conditions tested. We further apply the algorithm to experimental data obtained from tracking the centroid position of lymphocytes migrating under the effect of a laminar flow and from single myosin molecules interacting with actin in a dual-trap force-clamp configuration.The authors gratefully acknowledge financial support fromthe European Commission (FP7-ICT-2011-7, grant number 288263), Erasmus Mundus Doctorate Program Europhoton-ics (grant number 159224-1-2009-1-FR-ERA MUNDUS-EMJD), Spanish Ministry of Economy and Competi-tiveness (“Severo Ochoa” Programme for Centres of Excellence in Research & Development SEV-2015-0522,and FIS2014-56107-R grants), Generalitat de Catalunyathrough the CERCA program, Italian Ministry of Uni-versity and Research (FIRB “Futuro in Ricerca” 2013grant n. RBFR13V4M2 and Flagship Project NANOMAX),Fundaci ́o Privada CELLEX (Barcelona), Ente Cassa diRisparmio di Firenze, Human Frontier Science Program (GARGP0027/2012) and LaserLab Europe 4 (GA 654148). C.M.acknowledges funding from the Spanish Ministry of Econ-omy and Competitiveness (MINECO) and the EuropeanSocial Fund (ESF) through the Ram ́on y Cajal program 2015(RYC-2015-17896).Peer ReviewedPostprint (author's final draft

Assessment of SARS-CoV-2 RNA shedding in semen of 36 males with symptomatic, asymptomatic, and convalescent infection during the first and second wave of COVID-19 pandemic in Italy

: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), has been identified in the human testis, but the risk of transmission of SARS-CoV-2 through sexual intercourse still needs to be defined. The goal of our study was to determine if SARS-CoV-2 is detectable in the semen of patients suffering or recovering from coronavirus disease-19 (COVID-19), still testing positive at nasopharyngeal swabs but showing mild or no symptoms at the time of sampling. Detection of SARS-CoV-2 RNA in semen was performed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR targeting open reading frame (ORF) 1ab. Medical history of the enrolled patients was taken, including COVID-19-correlated symptoms, both at the time of diagnosis and at the time of interview. Results of real-time RT-PCR and nested PCR in semen showed no evidence of SARS-CoV-2 RNA in the 36 patients suffering or recovering from COVID-19 but still positive in a nasopharyngeal swab, from over 116 patients enrolled in the study. SARS-CoV-2 detection and persistence in semen would have an impact on both clinical practice and public health strategies, but our results would suggest that SARS-CoV-2 is not present in the semen of men recovering from COVID-19

Preliminary Results of ERAS Protocol in a Single Surgeon Prospective Case Series

Background and Objectives: The aim was to compare the intra and postoperative outcomes between the Enhanced Recovery After Surgery (ERAS) protocol versus the standard of care protocol (SCP) in patients who underwent radical cystectomy performed by a single surgeon. Materials and Methods: A retrospective comparative study was conducted including patients who underwent radical cystectomy from 2017 to 2020. Length of stay (LOS), incidence of ileus, early postoperative complications, and number of re-hospitalizations within 30 days were considered as primary comparative outcomes of the study. Results: Data were collected for 91 patients who underwent cystectomy, and 70 and 21 patients followed the SCP and ERAS protocol, respectively. The mean age of the patients was 70.6 (SD 9.5) years. Although there was a statistically significant difference in time to flatus (TTF) [3 (2.7-3) vs. 1 (1-2 IQR) days, p &lt; 0.001, in the SC hospital and in the ERAS center respectively], no difference was reported in time to first defecation (TTD) [5 (4-6) vs. 4 (3-5.8), p = 0.086 respectively]. The median LOS in the SCP group was 12 (IQR 11-13) days vs. 9 (IQR 8-13 p = 0.024). In the postoperative period, patients reported 22 complications (37% in SCP and 42.8% in ERAS group, p = 0.48). Conclusions: The study reveals how even partial adherence to the ERAS protocols leads to similar outcomes when compared to SCP. As a single surgeon series, our study confirmed the role of surgeons in reducing complications and improving surgical outcomes

State of the art in interstitial pneumonia with autoimmune features: a systematic review on retrospective studies and suggestions for further advances

The term interstitial pneumonia with autoimmune features (IPAF) has been proposed to define patients with interstitial lung disease (ILD) associated with autoimmune signs not classifiable for connective tissue diseases (CTDs). This new definition overcomes previous nomenclatures and provides a uniform structure for prospective studies through specific classification criteria.This work evaluates the characteristics of IPAF patients reported in the literature, to highlight potential limits through a comparative analysis and to suggest better performing classification criteria.Four retrospective studies on the IPAF population have been considered. The study subjects differed in age, sex, smoking habit, ILD pattern and outcomes. Another important difference lies in the diverse items considered in the classification criteria. The retrospective design of the studies and the absence from some of them of a rheumatologist clearly involved in the diagnosis may have influenced the data, but current IPAF criteria seem to include a rather heterogeneous population. To overcome these discrepancies, this review suggests a limitation in the use of single items and the exclusion of extremely specific CTD criteria. This should avoid the definition of IPAF for those diseases at different stages or at early onset. The investigation of a functional or morphological cut-off of pulmonary involvement would be useful

Management of acute behavioral disturbance in the Emergency Department: An Italian position paper from AcEMC, CNI-SPDC, SIP-Lo, SITOX

The phenomenon of acute behavioral disturbance is an underrecognized and potentially life-threatening syndrome, and sometimes an emergency in psychiatric settings. Patients presenting to the Italian emergency department (ED) with acute behavioral disturbances account for approximately 3.2% of all ED visits. The spectrum of behaviors and signs overlap with many clinical disease processes. In addition to patients with behavioral problems related to mental disorders or substance abuse, there is also a large group whose behavioral emergencies directly result from medical illness. The complexity of these patients, as well as the interdisciplinary nature of their care, requires a clear and consensual framework for care. A network of Italian scientific societies developed ten reccomendations for good clinical practice. The main purpose is to draw up a document that presents a standardized method for the organization of the care of patients with acute behavioral disorders in E

Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine-based high-dose chemotherapy regimen

High-dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third-generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR-HL accrued into a prospective registry-based study. Application of FEAM resulted in a 2-year progression-free survival (PFS) of 73·8% [95% confidence interval (CI), 0·64-0·81] with median PFS, overall survival and time to progression yet to be reached. The 2-year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12-0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose (18FFDG)-uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had 18FFDG-positrin emission tomography-positive lesions before HDT, the 2-year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12-0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR-HL patients typically pre-exposed to lung-damaging treatments