A real-world study of alemtuzumab in a cohort of Italian patients.

BACKGROUND AND PURPOSE: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. METHODS: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. RESULTS: We studied 322 patients (mean age 36.8 years, median EDSS score 3, median follow-up 1.94 years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p < 0.001). The number of previous-year relapses was associated with alemtuzumab ARR (adjusted risk ratio [RR] 1.38, p = 0.009). Progression-free survival was 94.5% after 1 year, and 89.2% after 2 years of alemtuzumab treatment. EDSS score improvement occurred in 13.5% after 1 year, and 20.6% after 2 years. Re-baselining patients after 6 months of alemtuzumab treatment, led to no evidence of disease activity status in 71.6% after 1 year and 58.9% after 2 years. CONCLUSIONS: Alemtuzumab decreases ARR independent of previous therapy, including patients with disease activity during natalizumab treatment. Overall, 90% of patients showed no disease progression, and 20% an improvement after 2 years of alemtuzumab.

Video calls during the COVID-19 pandemic: A bridge for patients, families, and respiratory therapists.

BACKGROUND: In response to COVID-19 pandemic outbreak, healthcare procedures and modalities have changed considerably. Video calls may supply valid support for health care professionals, contributing to maintaining the communication between hospitalized patients and their families. The present study aimed to observe the experience of a group of respiratory therapists who conducted video calls between patients and their families in a COVID-19 unit. METHOD: Semistructured interviews (20-30 minutes duration) with the respiratory therapists who conducted the video calls in a COVID-19 unit in the North of Italy were performed. Participants joined the study voluntarily and, after receiving the informed consent, the interviews were audio-recorded. To better understand healthcare professionals' experience, the Interpretive Description methodology was adopted. RESULTS: Seven respiratory therapists (three males, four females; mean age 45.1 ± 14.4) were recruited. Sixteen codes emerged from the analysis, constituting five primary themes: Contact, Impact, Challenges, Centering, and Future. CONCLUSIONS: The findings shed light on the usability of video calls during this emergency period and their potential for future implementation. Specifically, this type of call may bridge the distances in such periods of care and help professionals to emotionally support patients and caregivers. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cladribine vs other drugs in MS: Merging randomized trial with real-life data.

OBJECTIVE: Cladribine tablets were tested against placebo in randomized controlled trials (RCTs). In this study, the effectiveness of cladribine vs other approved drugs in patients with relapsing-remitting MS (RRMS) was compared by matching RCT to observational data. METHODS: Data from the pivotal trial assessing cladribine tablets vs placebo (CLARITY) were propensity score matched to data from the Italian multicenter database i-MuST. This database included 3,150 patients diagnosed between 2010 and 2018 at 24 Italian MS centers who started a disease-modifying drug. The annualized relapse rate (ARR) over 2 years from treatment start and the 24-week confirmed disability progression were compared between patients treated with cladribine and other approved drugs (interferon, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate), with comparisons with placebo as a reference. Treatment effects were estimated by the inverse probability weighting negative binomial regression model for ARR and Cox model for disability progression. The treatment effect has also been evaluated according to baseline disease activity. RESULTS: All weighted baseline characteristics were well balanced between groups. All drugs tested had an effect vs placebo close to that detected in the RCT. Patients treated with cladribine had a significantly lower ARR compared with interferon (relapse ratio [RR] = 0.48; p < 0.001), glatiramer acetate (RR = 0.49; p < 0.001), and dimethyl fumarate (RR = 0.6; p = 0.001); a similar ARR to that with fingolimod (RR = 0.74; p = 0.24); and a significantly higher ARR than natalizumab (RR = 2.13; p = 0.014), confirming results obtained by indirect treatment comparisons from RCTs (network meta-analyses). The relative effect of cladribine tablets 10 mg (cumulative dose 3.5 mg/kg over 2 years) was higher in patients with high disease activity vs all treatments except fingolimod and natalizumab. Effects on disability progression were largely nonsignificant, probably due to lack of power for such analysis. CONCLUSION: In patients with RRMS, cladribine tablets showed lower ARR compared with matched patients who started interferon, glatiramer acetate, or dimethyl fumarate; was similar to fingolimod; and was higher than natalizumab. The beneficial effect of cladribine tablets was generally amplified in the subgroup of patients with high disease activity. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with RRMS, cladribine-treated patients had lower ARR compared with interferon, glatiramer acetate, or dimethyl fumarate; similar ARR compared with fingolimod; and higher ARR compared with natalizumab.

Immune and central nervous system-related miRNAs expression profiling in monocytes of multiple sclerosis patients.

It is widely recognized that monocytes-macrophages adopt a wide variety of phenotypes, influencing the inflammatory activity and demyelination in Multiple Sclerosis (MS). However, how the phenotype of human monocytes evolves in the course of MS is largely unknown. The aim of our preliminary study was to analyse in monocytes of relapsing-remitting and progressive forms of MS patients the expression of a set of miRNAs which impact monocyte-macrophage immune function and their communication with brain cells. Quantitative PCR showed that miRNAs with anti-inflammatory functions, which promote pro-regenerative polarization, are increased in MS patients, while pro-inflammatory miR-155 is downregulated in the same patients. These changes may indicate the attempt of monocytes to counteract neuroinflammation. miR-124, an anti-inflammatory marker but also of myeloid cell quiescence was strongly downregulated, especially in progressive MS patients, suggesting complete loss of homeostatic monocyte function in the progressive disease phase. Profiling of miRNAs that control monocyte polarization may help to define not only the activation state of monocytes in the course of the disease but also novel pathogenic mechanisms.

First therapy choice in newly diagnosed Multiple Sclerosis patients: A multicenter Italian study.

BACKGROUND: The approval of an increasing number of disease modifying drugs for the treatment of Multiple Sclerosis (MS) creates new challenges for patients and clinicians on the first treatment choice. The main aim of this study was to assess factors impacting first therapy choice in a large Italian MS cohort. METHODS: Newly diagnosed relapsing-remitting (RR) MS patients (2010-2018) followed in 24 Italian MS centres were included in the study. We evaluated the association of baseline demographics, clinical and MRI characteristics to the first treatment choice by logistic regression models applied to pre-defined binary alternatives: dimethyl fumarate vs injectables (interferon and glatiramer acetate), teriflunomide vs injectables, fingolimod vs dimethyl fumarate and fingolimod vs natalizumab. RESULTS: We enrolled 3025 patients in the period between January 2010 and June 2018. Relapses in the previous year (OR = 2.75; p = 0.001), presence of spinal cord lesions (OR = 1.80; p = 0.002) and higher number (>9) of T2 lesions on the baseline brain MRI scan (OR = 1.65; p = 0.022) were the factors associated to dimethyl fumarate choice as first therapy vs an injectable drug. Older age (OR = 1.06; p < 0.001), male sex (OR = 2.29; p = 0.001) and higher EDSS (OR = 1.36; p < 0.001) were the factors associated with the choice of teriflunomide vs injectables. In more recent years, dimethyl fumarate (OR = 3.23; p < 0.001) and teriflunomide (OR = 2.53; p < 0.001) were chosen more frequently than injectables therapies. The main determinant for the choice of fingolimod as compared with dimethyl fumarate was a higher EDSS (OR = 1.56; p = 0.001), while there was a weak association with a longer disease duration (p = 0.068) and a longer time from onset to diagnosis (p = 0.085). Compared to fingolimod, natalizumab was preferred in patients with a younger age (OR = 0.95; p = 0.003) and higher EDSS (OR = 1.45; p = 0.007) and a shorter disease duration (OR = 0.52; p = 0.076). CONCLUSION: Many factors guided therapeutic decision for our Italian cohort of MS patients; they are mainly related to MS disease activity, baseline EDSS, disease duration and age.

Preterm birth: seven-year retrospective study in a single centre population.

BACKGROUND: Preterm birth is a health and social problem, considered the leading cause of neonatal mortality worldwide. It is associated with higher rates of neurodevelopmental morbidity, sensorineural impairments and other complications. The aim of the study was to describe the incidence and the major risk factors associated with preterm birth. METHODS: We performed a single center, observational and retrospective Cohort study in the Division of Obstetrics and Gynaecology, University Hospital "G. Martino", Messina. Clinical records of all pregnant women who delivered from 1st January 2010 to 31 of December 2016 were collected. RESULTS: In the 7 years considered, a total of 7954 pregnant women were included in our study. The majority of all preterm births were due to infants born late preterm (71.83%), 26.45% were due to preterm and 1.72% to extremely preterm. The preterm cohort had a higher proportion of history of preterm delivery (p < 0.0001), and unmarried (p = 0.003) and underweight or obese patients (p < 0.0001). In addition, prematurity was associated with presence of uterine anomalies (p < 0.0001), vaginal/urinary infections (p = 0.02), poli/oligohydramnios (p < 0.0001), maternal diabetes (p = 0.004), hypertension (p < 0.0001), short cervical length (p < 0.0001). CONCLUSIONS: We suggest prompt identification of all risk factors associated with preterm birth to apply immediate and appropriate specific interventions.

Determinants of therapy switch in multiple sclerosis treatment-naïve patients: A real-life study.

BACKGROUND: With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences. OBJECTIVES: To identify prognostic factors for early switch after first therapy choice. METHODS: Newly diagnosed relapsing-remitting MS patients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models. RESULTS: We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50; p = 0.009), natalizumab (HR = 0.13; p < 0.001), dimethyl-fumarate (HR = 0.60; p = 0.037), teriflunomide (HR = 0.21; p = 0.031) as compared to interferons. Younger age (HR = 0.96; p < 0.001), diagnosis delay (HR = 1.23; p = 0.021), higher baseline Expanded Disability Status Scale (HR = 1.17; p = 0.001), and spinal cord lesions (HR = 1.46; p = 0.001) were independently associated with higher inefficacy switch rates. We found lower switch for intolerance/safety with glatiramer acetate (HR = 0.61; p = 0.001), fingolimod (HR = 0.35; p = 0.002), and dimethyl-fumarate (HR = 0.57; p = 0.022) as compared to interferons, while it increased with natalizumab (HR = 1.43; p = 0.022). Comorbidities were associated with intolerance switch (HR = 1.28; p = 0.047). CONCLUSION: Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.

Effect of fingolimod action on the release of monocyte-derived microvesicles in multiple sclerosis patients.

Recently, microvesicles (MVs) were considered as important mediators of intercellular communication, especially in pathological conditions as Multiple Sclerosis (MS). In myeloid cells, MV shedding is induced by the receptor P2X7 with the involvement of acid sphingomyelinase (A-SMase) and release of the IL-1ß. In this study we evaluate how Fingolimod affects MVs production by the monocytes, as well as P2X7R, IL-1ß expression and A-SMase activity. Treatment decreased MVs production and IL-1ß expression. This effect was associated with the inhibition of A-SMase activity in BzATP-stimulated monocytes from MS patients. These evidences suggest monocyte MVs as a possible disease and drug-efficacy biomarkers.

Multiple Sclerosis Treatments Affect Monocyte-Derived Microvesicle Production.

Microvesicles (MVs) are released by immune cells especially of the myeloid lineage upon stimulation with ATP on its cognate receptor P2X7, both in physiological and pathological conditions. In multiple sclerosis (MS) the role of MVs remains little investigated. We aimed to compare the release of MVs in peripheral blood monocytes from MS patients with healthy donors (HDs) and to see how current MS treatment may affect such a production. We also assessed the treatment effect on M1 and M2 monocyte polarization and on the inflammasome components. Spectrophotometric quantification was performed to compare monocyte-derived MVs from 20 untreated relapsing-remitting MS patients and 20 HDs and to evaluate the effect of different treatments. Subgroups of nine interferon-beta and of five teriflunomide-treated MS patients were evaluated at baseline and after 2, 6, and 12 months of treatment. Six MS patients taking Fingolimod, after switching from a first-line therapy, were included in the study and analyzed only at 12 months of treatment. MVs analysis revealed that monocytes from MS patients produced vesicles in higher amounts than controls. All treatments reduced vesicle production but only teriflunomide was associated with a downregulation of purinergic P2X7 receptor and inflammasome components expression. The therapies modulated mRNA expression of both M1 and M2 monocyte markers. Our results, suggesting new molecular targets for drugs currently used in MS, may potentially provide useful novel evidence to approach the disease.

Low prevalence of hepatitis B and hepatitis C virus serum markers in a cohort of pregnant women from Southern Italy.

BACKGROUND: Mother-to-child transmission is still considered a major factor in the spread of hepatitis viruses. Nevertheless, epidemiological data on hepatitis B virus (HBV) and hepatitis C virus (HCV) in reproductive-age women are limited even in areas like the South of Italy where both viruses had been widespread. AIM: The aim of this study was to investigate the prevalence of HBV and HCV serum markers in a large cohort of pregnant women from Southern Italy. METHODS: Data concerning 7558 pregnant women consecutively admitted to an Obstetric Division of a Sicilian University Hospital over a six-year period (January 2010-December 2015) were retrospectively collected from clinical notes. RESULTS: Positivity for both HBV s-antigen (HBsAg) and antibodies to HCV (anti- HCV) was very low (0.5% and 0.2%, respectively). HBsAg prevalence was significantly higher in non-Italian than in Italian women (p<0.001). On the contrary, all the anti-HCV positive cases were of Italian origin. Age was not significantly different between positive and negative women. CONCLUSION: These results confirm the dramatic decline of HBV and HCV prevalence that recently occurred in Southern Italy, and highlight the importance and cost-effectiveness of systematic HBV and HCV screening in childbearing age women in order to properly apply the available preventive measures and definitively eliminate the risk of vertical transmission for both viruses.

Thromboembolism prophylaxis in laparoscopic surgery for gynecologic benign diseases. Results of a single center experience in 922 procedures.

AIM: The aim of this study is to assess the role of preoperative evaluation risk for venous tromboembolism (VTE) in patients submitted to laparoscopic surgery for gynecologic benign diseases. METHODS: Date from nine hundred twenty-two women affected by adnexal benign diseases treated with laparoscopic procedures were collected and included in this study. VTE risk was assessed by "on line Caprini score calculator". Patients with one or more negative risk factors for Caprini's score underwent to venous thromboembolism prophylaxis (VTP). The remainign of the patients did not recived any VTP. A survey was conducted after three months from the discharge in order to collect the follow up date. RESULTS: In our study 160 patients had a Caprini's score major than 2 and they have been subjected to VTP. A total of 762 patients were considered at low risk for VTE and they did not receive any VTP. In these patients was not registered any event of VTE. DISCUSSION: The results of this study suggest that laparoscopic approach, when carried out in non-oncological patients and without any previous thromboembolic risk factor, is associated with a very low risk of VTE. This study also confirm what was reported by Ageno et al. 6, Nick et al. 7 and ACCP guidelines in 2012 8 in which routine thromboprophylaxis is recommended for patients with additional risk factors. CONCLUSIONS: Laparoscopic surgery in women for gynecologic benign diseases is associated with a very low risk of thromboembolism and therefore it does not require any mechanical or pharmacological thromboprophylaxis in the absence of risk factors. The systematic evaluation of VTE risk with the help of a standard calculator is highly recommended. KEY WORDS: Gynaecology, Laparoscopic surgery, Thromboprophylaxis.

Data comparison between pharmacological induction of labour and spontaneous delivery. A single centre experience.

OBJECTIVES: To assess the differences in the maternal and fetal outcomes between pharmacological induced and sponta-neous labour in nulliparous women. MATERIAL AND METHODS: Observational cohort study carried out over a period of 2 years. INCLUSION CRITERIA: nulliparous sin-gleton pregnancies, with cephalic fetal presentation, elective labour induction with intra-vaginal prostaglandin E2 (PGE2) gel (Prepidil® 2 mg) at a gestational age of 41 weeks. CONTROL GROUP: patients who entered labour spontaneously at a gestational age of ≥ 40 weeks. The main demographic maternal characteristics and intra- and postpartum data were extracted from computer records and obstetrics diaries and were used for the analysis. RESULTS: One hundred and three patients with induction of labour and 97 with spontaneous labour were enrolled. Cesarean delivery was performed in 18 cases (17.5%), all in the induction group. There were no differences in newborn weights between the 2 groups while both the 1-minute and 5-minute Apgar scores were significantly higher in the spontaneous group (p = 0.014 and p = 0.0003, respectively). Women in the induction group had a significantly longer duration of I stage labour in comparison with spontaneous group (p < 0.0001). CONCLUSIONS: Primiparous women whose labour was induced spent a longer time in labour than women who presented in spontaneous labour. Clinicians should keep in mind that a slow rate of dilation in a woman being induced may be normal. For this reason, an arrest diagnosis needs to be carefully considered.

Full-Thickness Excision versus Shaving by Laparoscopy for Intestinal Deep Infiltrating Endometriosis: Rationale and Potential Treatment Options.

Endometriosis is defined as the presence of endometrial mucosa (glands and stroma) abnormally implanted in locations other than the uterine cavity. Deep infiltrating endometriosis (DIE) is considered the most aggressive presentation of the disease, penetrating more than 5 mm in affected tissues, and it is reported in approximately 20% of all women with endometriosis. DIE can cause a complete distortion of the pelvic anatomy and it mainly involves uterosacral ligaments, bladder, rectovaginal septum, rectum, and rectosigmoid colon. This review describes the state of the art in laparoscopic approach for DIE with a special interest in intestinal involvement, according to recent literature findings. Our attention has been focused particularly on full-thickness excision versus shaving technique in deep endometriosis intestinal involvement. Particularly, the aim of this paper is clarifying from the clinical and methodological points of view the best surgical treatment of deep intestinal endometriosis, since there is no standard of care in the literature and in different surgical settings. Indeed, this review tries to suggest when it is advisable to manage the full-thickness excision or the shaving technique, also analyzing perioperative management, main complications, and surgical outcomes.

Thyroid diseases in pregnancy: a current and controversial topic on diagnosis and treatment over the past 20 years.

BACKGROUND: Management of thyroid diseases during pregnancy requires special considerations because maternal thyroid diseases can have adverse effects on both pregnancy and fetus. Universal screening for thyroid diseases in pregnant women is not currently supported by studies with high evidence whereas guidelines have been released for individuals at high risk, although controversies are still in debate. Iodine prophylaxis should be performed systematically to women during pregnancy. MATERIALS AND METHODS: An electronic search of PubMed/Medline and EMBASE concerning thyroid diseases and pregnancy have been conducted over the past 20 years and summarized. RESULTS: Data regarding prevention and treatment of thyroid diseases during pregnancy are reported from analysis of the literature. CONCLUSIONS: As thyroid dysfunction may cause profound impact on mother's and fetus's health, implementation by strict application of clinico-diagnostic flowchart and recommendations is of paramount importance when dealing with thyroid diseases during pregnant state.

Would it be too late? A retrospective case-control analysis to evaluate maternal-fetal outcomes in advanced maternal age.

PURPOSE: To evaluate maternal-fetal outcomes in women of advanced maternal age (AMA; >35 years old) and women of physiological maternal age as controls (C; <35 years old). METHODS: Single-center, retrospective case-control analysis, from January 1 to December 31, 2013. For each group, we evaluated obstetric history, number of twin pregnancies, delivery mode, incidence of obstetric diseases and neonatal outcomes (5-min Apgar score, neonatal weight, meconium stained fluid rate, admission to the neonatal intensive care unit rate, and incidence of congenital malformations). Data are presented as n (%) and analyzed with χ (2) test and Fisher exact test (when required). A p value < 0.05 was considered statistically significant. Moreover, we calculated the odds ratio (OR), with confidence interval (CI) at 95 %. RESULTS: We enrolled 1,347 pregnant women, 210 (15.6 %) in AMA and 1,137 (84.4 %) C. AMA patients showed a higher rate of previous (anamnestic) spontaneous abortion (SA; p = 0.001; OR = 2.10) and previous (anamnestic) voluntary pregnancy termination (p = 0.022; OR = 1.59), iterative cesarean section (p = 0.026; OR = 2.33), SA (p = 0.001; OR = 12.82), preterm delivery (p = 0.001; OR = 69.84), congenital malformations (p = 0.036; OR = 3.94). In C there was a greater number of nulliparous (p = 0.009; OR = 0.52) and vaginal deliveries (p = 0.025; OR = 0.41). There were not any statistically significant differences between the two groups for twin pregnancies (p = 0.862; OR = 0.97), first cesarean section (p = 0.145; OR = 0.95), other obstetric diseases and neonatal outcomes. CONCLUSION: AMA could be considered an important risk factor only for SA and PTD and does not influence neonatal outcomes except for congenital malformations.

Sjögren's syndrome associated with antiphospholipid syndrome and fetal myocardial echogenicity: case report.

INTRODUCTION: Sjögren's syndrome is a rare systemic autoimmune disorder associated with pregnancy (0.3-0.6%). The typical occurrence of anti-Ro/SSA and anti-La/SSB autoantibodies in the maternal serum can modify the perinatal outcome: neonatal lupus and congenital heart block are the most common fetal complications. CASE: we report a case of pregnancy complicated by a secondary form of SS associated with antiphospholipid syndrome and fetal myocardial echogenicity. CONCLUSION: in conclusion, increased attention must be paid to pregnancies associated with autoimmune disorders, since careful ultrasonographic and clinical monitoring and preventive treatment with corticosteroids could minimize severe and common fetal complications.

An unusual form of mirror syndrome: a case report.

AIM: Mirror syndrome is a triad consisting of fetal hydrops, maternal edema and placentomegaly. Its pathogenesis is unclear and it is frequently mistaken for preeclampsia, even though distinguishing features can be identified. It is associated with an increase in fetal mortality and maternal morbility. METHODS: We report an uncommon case of mirror syndrome, which appeared late in pregnancy (38 weeks) in a young nulliparous and characterized by sudden and massive vulvar edema, with placentomegaly and hydramnios but without fetal hydrops. RESULTS: Our report is an interesting example of an unusual form of Mirror syndrome for several reasons. First of all, the gestational age in which the disorder appeared differs remarkably from the data of literature; in our case, clinical signs and symptoms appeared only at 37 weeks. Another difference consists in the lack of hypertension that represents the second most common symptom associated and explains the difficulty to differentiate this syndrome from preeclampsia. CONCLUSIONS: Although mirror syndrome is associated with an increase in perinatal mortality, in the case we reported the late onset of the disorder associated with the medical treatment and the timely decision to perform a caesarean section allowed the birth of a healthy baby.

The influence of planned kinds of delivery on pregnant women's emotional state.

OBJECTIVE: To evaluate if labour induction and elective caesarean section could influence anxiety and depression in pregnant women. METHODS: One hundred and sixteen consecutive pregnant women with uncomplicated singleton pregnancy at term, scheduled for these two obstetric procedures were enrolled. An anonymous questionnaire with two self-rating instruments STAI and HAM-A for anxiety and HAM-D for depression was administered. RESULTS: Anxiety levels did not show significant differences while a light depressive mood was evidenced among pregnant women waiting for labour induction (p = 0.01). CONCLUSIONS: An adequate psychological support could be considered a helpful tool for pregnant women scheduled for labour induction.