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In this retrospective, multicenter, real-world study we collected clinical and magnetic resonance imaging (MRI) data of all patients (n = 40) with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab according to a "free-of-charge" protocol available before the drug marketing approval in Italy. Almost all (39/40) started alemtuzumab after discontinuing multiple disease-modifying treatments (DMTs) because of either lack of response or safety concerns. We considered the proportion of alemtuzumab-treated patients who had no evidence of disease activity (NEDA-3) and disability improvement over a 36-month follow-up period. NEDA-3 was defined as absence of relapses, disability worsening, and MRI activity. Disability improvement was defined as a sustained reduction of ≥ 1-point in Expanded Disability Status Scale (EDSS) score. At follow-up, 18 (45%) patients achieved NEDA-3, 30 (75%) were relapse-free, 33 (82.5%) were EDSS worsening-free, and 25 (62.5%) were MRI activity-free. Eleven (27.5%) patients had a sustained disability improvement. We found no predictor for the NEDA-3 status, while the interaction of higher EDSS score by higher number of pre-alemtuzumab relapses was associated with a greater chance of disability improvement (odds ratio 1.10, p = 0.049). Our study provides real-world evidence that alemtuzumab can promote clinical and MRI disease remission, as well as disability improvement, in a significant proportion of patients with RRMS despite prior multiple DMT failures. The drug safety profile was consistent with data available from clinical trials.

In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs). The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999. Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C. pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children with M. pneumoniae and/or C. pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.

Hepatic intra-arterial chemotherapy (HIAC) leads to a higher response rate than systemic administration in untreated patients with liver metastases from colorectal cancer (CRC). The aim of this study was to evaluate the activity and safety of giving HIAC through a percutaneous catheter in pre-treated patients.Forty-five CRC patients with liver-only or liver-dominant metastases, resistant or refractory to previous systemic therapy, were treated using a temporary trans-subclavian catheter. A 3-day chemotherapy regimen of daily 5-fluorouracil (5-FU) 1000 mg/m2/day + heparin 5000 IU/day given as a 24-hour continuous infusion, and twice daily bolus injections of cisplatin (CDDP) 10 mg/m2 and mitomycin C (MMC) 2 mg/m2, was administered every six weeks.One hundred and seventeen courses were administered to 45 patients (a median of three per patient: range 1-5). Of the 44 patients evaluable for response, 16 (35%) had a partial response, 15 (33%) stable disease and 12 (26%) progressive disease. Eleven of the 16 responding patients had been refractory to a previous 5-FU-based systemic therapy. The most relevant grade 3-4 toxicities included neutropenia (22%) and thrombocytopenia (15%). Gastro-duodenal ulcers occurred in nine patients. Catheter displacement was recorded during 22 out of 117 (18%) courses.HIAC with 5-FU, CDDP and MMC given through a temporary percutaneous catheter is safe and active in pretreated patients with metastatic CRC. Iatrogenic gastroduodenal ulcers are a serious but manageable complication.

Various percentages of iatrogenic gastroduodenal ulcers during hepatic intra-arterial chemotherapy have been reported in the literature. The aim of this study was to analyze a homogeneous cohort of patients in order to evaluate the evolution and management of this complication.We retrospectively reviewed the clinical charts of 80 patients with primary or metastatic liver tumors who received 186 hepatic arterial infusion chemotherapy courses of 5-fluorouracil, cisplatin and mitomycin-C. All of the patients complaining of upper gastrointestinal symptoms during or after hepatic arterial infusion underwent esophagogastroduodenoscopy.Esophagogastroduodenoscopy was performed in 14 patients, all of whom had gastroduodenal ulcers. Two of ten investigated patients were Helicobacter pylori positive. All of the patients were treated with a proton pump inhibitor and five also received major analgesics. All of the ulcers healed without complications. Six patients did not continue with hepatic arterial infusion for reasons other than ulcers. Eight patients received a subsequent hepatic intra-arterial chemotherapy course, five despite the persistence of an active ulcer.Iatrogenic gastroduodenal ulcers are probably due to ischemia and the direct toxicity of the anticancer agents. They are Helicobacter pylori independent and do not represent an absolute contraindication for the continuation of hepatic intra-arterial chemotherapy.

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.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.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.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.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.Gynaecology, Laparoscopic surgery, Thromboprophylaxis.La valutazione del rischio tromboembolico in pazienti che verranno sottoposti a chirurgia addominale rimane un prerequisito fondamentale nell’ottica di ridurre i rischi correlati ad una inadeguata profilassi. Nello specifico, le pazienti sottoposte a chirurgia laparoscopica per patologia annessiale benigna sono spesso considerate a priori a basso rischio tromboembolico. Infatti solitamente ci si trova di fronte a paziente con età inferiore a 40 anni con scarse se non assenti comorbidità e che dovranno subire una procedura rapida e relativamente atraumatica. Non essendoci però forti evidenze scientifiche a riguardo ed essendo comunque presente, seppur basso, un rischio di sviluppare tromboembolia post-operatoria, abbiamo voluto analizzare 922 pazienti operate presso la nostra struttura per patologia annessiale benigna. Di queste 762 sono state considerate a basso rischio per eventi trombo embolici. Tramite l’ausilio dello score di Caprini, abbiamo eseguito una valutazione preoperatoria delle pazienti confermando così il teorico basso rischio tromboembolico. In queste pazienti non è stata eseguita nessuna profilassi (medica o meccanica). È stato poi eseguito un follow up adeguato che ha confermato l’assenza di eventi tromboembolici in queste pazienti. I risultati della nostra esperienza ci consentono di meglio identificare le pazienti a reale basso rischio tromboembolico che dovranno essere operate con tecnica laparoscopica per patologia annessiale benigna.

Background and purpose There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself or whether it is due to the natural course of highly active multiple sclerosis (MS). Our aim was to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS. Methods Patients with relapsing-remitting MS who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis. Results A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Amongst these patients, five (5%) had a reactivation that was considered to be a rebound. Conclusions The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described.

OBJECTIVE: The effects of carbonated beverages on the gastrointestinal tract have been poorly investigated. Therefore, this study aims to assess the effect of carbonated water intake in patients with functional dyspepsia and constipation. METHODS: Twenty-one patients with dyspepsia and secondary constipation were randomized into two groups in a double-blind fashion. One group (10 subjects) drank carbonated water and the other (11 subjects) tap water for almost 15 days. Patients were evaluated for dyspepsia and constipation scores, and underwent a satiety test by a liquid meal, radionuclide gastric emptying, sonographic gallbladder emptying and colonic transit time, using radio-opaque markers. RESULTS: The dyspepsia score was significantly reduced with carbonated water (before = 7.9 +/- 2.8 after = 5.4 +/- 1.7; 0.05) and remained unmodified after tap water (9.7 +/- 5.3 9.9 +/- 4.0). The constipation score also decreased significantly ( 0.05) after carbonated water (16.0 +/- 3.9 12.1 +/- 4.4; 0.05) and was not significantly different with tap water (14.7 +/- 5.1 13.7 +/- 4.7). Satiety was significantly reduced with carbonated water (before = 447 +/- 146 kcal after = 590 +/- 245; 0.01). Gallbladder emptying (delta percent contraction) was significantly improved only with carbonated water (39.9 +/- 16.1% 53.6 +/- 16.7%; 0.01). CONCLUSION: In patients complaining of functional dyspepsia and constipation, carbonated water decreases satiety and improves dyspepsia, constipation and gallbladder emptying

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).

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

ObjectiveCladribine 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.MethodsData 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.ResultsAll 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.ConclusionIn 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 evidenceThis 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.

The LUMIRA trial evaluated the effectiveness of radiofrequency (RFA) and microwave ablation (MWA) in lung tumours ablation and defining more precisely their fields of application. It is a controlled prospective multi-centre random trial with 1:1 randomization. Fifty-two patients in stage IV disease (15 females and 37 males, mean age 69 y.o., range 40–87) were included. We randomized the patients in two different subgroups: MWA group and RFA group. For each group, we evaluated the technical and clinical success, the overall survival and complication rate. Inter-group difference was compared using Chi-square test or Fisher’s exact test for categorical variables and one-way ANOVA test for continuous variables. For RFA group, there was a significant reduction in tumour size only between 6 and 12months (p value=0.0014). For MWA group, there was a significant reduction in tumour size between 6 and 12months (p value=0.0003) and between pre-therapy and 12months (p value=0.0215). There were not significant differences between the two groups in terms of survival time (p value=0.883), while the pain level in MWA group was significantly less than in RFA group (1.79&nbsp

We report the final results of a prospective trial testing the combination of fludarabine, Ara-C and idarubicin (FLAI) followed by low-dose gemtuzumab ozogamicin (FLAI-GO) in 85 patients aged 60 years or more with CD33+ acute myeloid leukaemia (AML). Median age was 68 years (60-82); karyotype was unfavourable in 21 patients (24 %), intermediate in 63 (74 %) and favourable in 1 (2 %). There were five therapy-related deaths. Of the 80 evaluable patients, 47 achieved complete response (CR) (58 %); CR rates were 65 and 32 % in good-intermediate/poor karyotype patients, respectively. Median length of CR was 7 months (3-76). The cumulative incidence of relapse was 84 % with an actuarial survival of 50.3 % at 1 year and 14.4 % at 2 years. The study control population is an unselected consecutive historic cohort of 104 patients treated with the FLAI regimen, who were matched for age and prognostic factors. CR rates after FLAI-GO and FLAI were comparable. However, patients with de novo AML and intermediate-favourable karyotype receiving GO had a significantly lower risk of relapse at 2 years as compared to patients not receiving GO (n = 77) (40 vs 80 %, p = 0.01) and significantly better disease-free survival (p = 0.018) and overall survival (p = 0.022).

Submicroscopic copy-number variations make a considerable contribution to the genetic etiology of human disease. We have analyzed subjects with idiopathic mental retardation (MR) by using whole-genome oligonucleotide-based array comparative genomic hybridization (aCGH) and identified familial and de novo recurrent Xp11.22-p11.23 duplications in males and females with MR, speech delay, and a peculiar electroencephalographic (EEG) pattern in childhood. The size of the duplications ranges from 0.8-9.2 Mb. Most affected females show preferential activation of the duplicated X chromosome. Carriers of the smallest duplication show X-linked recessive inheritance. All other affected individuals present dominant expression and comparable clinical phenotypes irrespective of sex, duplication size, and X-inactivation pattern. The majority of the rearrangements are mediated by recombination between flanking complex segmental duplications. The identification of common clinical features, including the typical EEG pattern, predisposing genomic structure, and peculiar X-inactivation pattern, suggests that duplication of Xp11.22-p11.23 constitutes a previously undescribed syndrome.

We conducted a long-term follow-up retrospective study on 91 consecutive newly diagnosed acute promyelocytic leukaemia (APL) patients. Induction and consolidation therapy were well-tolerated by most patients. Of the 79 patients who were initially treated with the all-trans retinoic acid (ATRA)-containing regimens, there were 3 haemorrhagic deaths during the first period of therapy (4%) and one in consolidation which was due to infection. Following consolidation, molecular assessment of response was performed on 67 patients, and 66 were found to have achieved cytogenetic and molecular remission (98%). After a median follow-up of 100 months (12-192), 10 of the 75 patients who achieved complete remission (13%) relapsed. Seventy-eight percent of the patients were expected to be alive at 14 years from diagnosis, i.e., 90 and 48% of patients of intermediate-low risk and high risk at presentation, respectively (p=0.0009). Sixty-nine patients were in molecular remission after first-line and/or salvage therapy (74%). To date, 4 patients out of the 91 have undergone salvage allogeneic transplant (4%).

Introduction: Patients with constipation often report dyspeptic symptoms, but whether constipation is associated with specific dyspeptic symptoms and altered gastrointestinal (GI) motility, remains to be established. Our aim was to study symptoms association and GI motility parameters in patients with constipation and functional dyspepsia. Patients and Method: 42 patients with different symptoms and severity of constipation and dyspepsia were enrolled. Scintigraphic gastric emptying, colonic transit time and gallbladder contraction were studied in all subjects. Results: No significant association was observed between individual symptoms of constipation and dyspepsia. Patients with more severe constipation did not have higher dyspepsia severity scores. Colonic transit time, gastric half emptying and gallbladder contraction were not significantly correlated. Although patients with severe nausea had faster colonic transit than those with absent/mild symptom (19 ± 2 vs. 48 ± 7 h; p < 0.05), the multivariate analysis only revealed a significant association between severe postprandial fullness, delayed t1/2 (OR 1.05, CI 1–1.1) and impaired gallbladder contraction (OR 0.94, CI 0.89–0.99). Conclusions: Constipation was not associated with severity, or any particular dyspeptic symptom. Although motor abnormalities of both colon and proximal GI tract regions existed in the subset of constipated dyspeptic patients, they did not seem associated with the genesis of different dyspeptic symptoms.

It has recently been demonstrated that patients with Angelman's syndrome who exhibited a deletion on cytogenetic tests show more severe clinical pictures with drug-resistant epilepsy than patients with Angelman's syndrome not carrying the deletion. To verify if this difference in clinical severity can be attributed to genes for the three γ-aminobutyric acid (GABA)A receptor subunits ( GABRB3, GABRA5, GABRG3) located in the deleted region, a possible modification of peripheral markers of the GABAergic system was investigated in 12 subjects with Angelman's syndrome and 20 age-matched subjects (8 with idiopathic epilepsy and 12 not affected by neurologic diseases). The results confirmed a more severe clinical picture, and epilepsy syndrome in particular, in Angelman's syndrome patients with deletions versus patients without deletions. In contrast, biochemical study (based on dosage of plasma levels of GABA and diazepam binding inhibitor, an endogenous ligand of GABAA and peripheral benzodiazepine receptors, showed contradictory results: patients with Angelman's syndrome showed significantly higher levels of GABA and diazepam binding inhibitor than patients without neurologic impairment but significantly lower levels than epileptic controls. ( J Child Neurol 2003; 18: 21—25).

BACKGROUND: After the eradication of Helicobacter pylori, an increased incidence of gastroesophageal reflux disease and acid gastric secretion have been reported. AIM: To evaluate the effect of Helicobacter pylori-eradication on proximal and distal gastroesophageal reflux and acid clearance in patients with gastroesophageal reflux disease. PATIENTS AND METHODS: Sixty-eight gastroesophageal reflux disease patients (age range 18-61 years) were studied by upper endoscopy. All underwent esophageal manometry and dual probe 24-h pH-metry. RESULTS: Percent of time at pH

The rapid pull-through (RPT) technique during esophageal manometry helps to identify various pressure profiles of hiatal hernia (HH), based on the presence of two high pressure zones: the diaphragmatic crura (DC) and the lower esophageal sphincter (LES). Our aim was to correlate different HH profiles with frequency of reflux episodes in patients with gastroesophageal reflux disease (GERD). Seventy-eight patients with GERD and HH underwent esophageal manometry with RPT and were grouped according to the prevalent pressure profile of HH. Twenty-four-hour pH-metry served to quantify traditional (TR) and nontraditional refluxes (drop of 1 pH unit with pH > 4 or pH < 4 and time < 5 sec) (NTR) during total, upright, and recumbent periods. The group with a prevalent "flat" HH profile, representing LES and DC impairment, had significantly more TRs in total time of reflux (P < 0.01) and in recumbent and upright periods (P < 0.05) compared to the group with a prevalence of the two pressure peaks, corresponding to LES and DC efficiency. However, the group with the flat profile had significantly more NTRs + TRs than the group with pressure peaks in total time (P < 0.01) and recumbent position (P < 0.001) but not in the upright position. Hiatal hernia predisposes to GERD, but only the associated impairment of the LES and diaphragmatic crura pressures represents a condition of high risk for gastroesophageal reflux events

BACKGROUND: The correlation between symptoms and observed impaired function in functional dyspepsia is still inconsistent. The aims of the study were to obtain a measure of satiety by a meal test; to verify whether this compares with severity of symptoms assessed using a reproducible questionnaire; and to correlate the parameters of satiety test and gastric emptying with all the dyspeptic symptoms. METHODS: Fifty-two functional dyspepsia patients reported their symptoms on a standardized questionnaire that considered belching, bloating, early satiety, epigastric pain and burning, nausea, postprandial fullness and vomiting. They were monitored for gastric emptying of a solid caloric meal using a radionuclide technique and underwent a test to quantify meal-induced satiety by a liquid caloric meal. RESULTS: The number of kilocalories ingested during the satiety test until the occurrence of maximum satiety in healthy subjects was 110% higher than in the dyspeptic group (mean +/- s(mean): 1110 +/- 23 versus 532 +/- 56; P < 0.01). We found a significant positive correlation between gastric emptying rate and kcal of the satiety test (P < 0.01; r = 0.428). Logistic regression showed a significant inverse association between severity of early satiety-coded as absent, mild, moderate or severe, kcal of meal test (P = 0.01), and gastric emptying lag phase (P = 0.03). Bloating was associated directly with t(1/2) of gastric emptying (P = 0.03) and inversely with lag phase (P = 0.02). CONCLUSIONS: The satiety test gives a fine numerical measure of satiety and confirms the results of a symptoms questionnaire. Our study showed an indirect correlation between severity of early satiety--as measured by the satiety test, and gastric emptying rate, as well as an association between bloating and delayed gastric emptying