Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML). The objective is to evaluate the noninferiority of the ...efficacy of an extended interval dosing (EID) compared with the standard interval dosing (SID) of natalizumab. It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Three hundred and sixty patients were enrolled. Median dose interval (MDI) following 24th infusion was 4.7 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Two hundred and sixteen patients were in the SID group (MDI = 4.3 weeks) and 144 in the EID group (MDI 6.2 weeks). Annualized relapse rate was 0.060 (95% CI = 0.033–0.087) in the SID group and 0.039 (95% CI = 0.017–0.063) in the EID group. The non-inferiority of EID
versus
SID was satisfied. In conclusion, there is no evidence of a reduced efficacy of natalizumab in an EID setting. This observation confirms previous results and together with the emerging evidence of a reduced risk of PML associated to an EID, supports the need of a randomized study to assess the need to change the standard of the natalizumab dosing schedule.
Background:
Leptomeningeal enhancement (LME) has been described as a biomarker of meningeal inflammation in multiple sclerosis (MS).
Objective:
The aim of this study was to (1) assess if LME is ...predictive of disability worsening in progressive MS (pMS) patients and (2) investigate the pathological substrates of LME in an independent post-mortem MS series.
Methods:
In total, 115 pMS patients were imaged yearly with 1.5T MRI, using post-contrast CUBE 3D FLAIR for LME detection. Endpoint: to identify the baseline variables predictive of confirmed disability worsening (CDW) at 24 months follow-up. Post-mortem, inflammation, and structural changes of the leptomeninges were assessed in 12 MS/8 control brains.
Results:
LME (27% of patients at baseline) was associated with higher EDSS and lower brain volume (nBV). LME was unchanged in most patients over follow-up. LME at baseline MRI was independently associated with higher risk of 24 months CDW (HR 3.05, 95% CI 1.36–6.84, p = 0.007) in a Cox regression, including age, nBV, T2 lesion volume, high-efficacy treatments, and MRI disease activity. Post-mortem, focal structural changes (fibrosis) of the leptomeninges were observed in MS, usually associated with inflammation (Kendall’s Tau 0.315, p < 0.0001).
Conclusions:
LME is frequently detected in pMS patients using 1.5T MRI and is independently predictive of disability progression. LME could result from both focal leptomeningeal post-inflammatory fibrosis and inflammation.
To minimize the risk of Progressive Multifocal Leukoencephalopathy and rebound in JCV-positive multiple sclerosis (MS) patients after 24 natalizumab doses, it has been proposed to extend the ...administrations interval. The objective is to evaluate the EID efficacy on MRI activity compared with the standard interval dosing (SID).
Observational, multicentre, retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Three hundred and sixteen patients were enrolled. The median dose interval (MDI) following the 24th infusion was 5 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Patients were grouped into 2 categories according to the mean number of weeks between doses: <5 weeks, SID; ≥5 weeks, EID.
One hundred and eighty-seven patients were in the SID group (MDI = 4.5 weeks) and 129 in the EID group (MDI 6.1 weeks). The risk to develop active lesions on MRI is similar in SID and EID groups during the 6 and 12 months after the 24th natalizumab infusion, respectively 4.27% (95% CI:0.84–7.70) vs 4.71% (95% CI:0.16–9.25%) p = 0.89 and 8.50% (95% CI:4.05–12.95) vs 6.55% (95% CI:2.11–11.00%) p = 0.56. The EID regimen does not appear to increase the occurrence of MRI activity during follow-up.
There is no evidence of the reduced efficacy of natalizumab in an EID setting regarding the MRI activity. This observation supports the need for a bigger randomized study to assess the need to change the standard of the natalizumab dosing schedule, to better manage JCV-positive patients.
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•Extending the natalizumab interval dose over 4 weeks could reduce Progressive Multifocal Leukoencephalopathy risk.•Extending the administrations interval of natalizumab could increase MRI activity.•In our observational, multicentre, retrospective cohort study over 316 patients with multiple sclerosis, showed that the extended dose regimen does not increase the occurrence of MRI activity after 6 and 12 months.•The extended dose natalizumab regimen could maintain the natalizumab efficacy and could be a useful dosing schedule in JCV-positive patients.
Background
The relationship between dietary habits and multiple sclerosis (MS) risk is still controversial. Most studies have involved populations from Scandinavia, North America, and Australia. Data ...on populations from southern Europe (an area of high MS prevalence) are scarce.
Objective
To examine the association between dietary habits/nutritional status and risk of a first demyelinating event, in a southern European incident cohort.
Methods
In this incident case-control study, a detailed nutritional assessment was performed by a registered dietitian in patients with a first demyelinating event, and in age-/sex-matched controls. Body composition analysis, anthropometric evaluation, and blood tests for nutritional status were also performed.
Results
Eighty-three patients with a first demyelinating event were prospectively recruited over a 1-year period. Low intake of fibers (OR 0.846,
p
= 0.014), vitamin D (OR 0.730,
p
< 0.0001), and alpha-linolenic acid (OR 0.283,
p
= 0.014), high BMI (OR 1.132,
p
= 0.028), and ever smoker status (OR 4.472,
p
= 0.003) were all independently associated with risk of a first demyelinating event. Higher intake of rapid absorption carbohydrates, lower intake of vegetal proteins, and higher intake of animal proteins were observed in patients with a first demyelinating event.
Conclusions
Significant differences between patients and controls are observed in the dietary habits at the time of a first demyelinating event, suggesting low intake of fibers, vitamin D and alpha-linolenic acid as the main dietary risk factors. Furthermore, high cardiovascular risk dietary habits are frequent at the time of MS onset, suggesting the usefulness of nutritional intervention as part of the activities of MS centers.
Background
A new manometric classification of esophageal achalasia has recently been proposed that also suggests a correlation with the final outcome of treatment. The aim of this study was to ...investigate this hypothesis in a large group of achalasia patients undergoing laparoscopic Heller–Dor myotomy.
Methods
We evaluated 246 consecutive achalasia patients who underwent surgery as their first treatment from 2001 to 2009. Patients with sigmoid-shaped esophagus were excluded. Symptoms were scored and barium swallow X-ray, endoscopy, and esophageal manometry were performed before and again at 6 months after surgery. Patients were divided into three groups: (I) no distal esophageal pressurization (contraction wave amplitude <30 mmHg); (II) rapidly propagating compartmentalized pressurization (panesophageal pressurization >30 mmHg); and (III) rapidly propagating pressurization attributable to spastic contractions. Treatment failure was defined as a postoperative symptom score greater than the 10th percentile of the preoperative score (i.e., >7).
Results
Type III achalasia coincided with a longer overall lower esophageal sphincter (LES) length, a lower symptom score, and a smaller esophageal diameter. Treatment failure rates differed significantly in the three groups: I = 14.6% (14/96), II = 4.7% (6/127), and III = 30.4% (7/23;
p
= 0.0007). At univariate analysis, the manometric pattern, a low LES resting pressure, and a high chest pain score were the only factors predicting treatment failure. At multivariate analysis, the manometric pattern and a LES resting pressure <30 mmHg predicted a negative outcome.
Conclusion
This is the first study by a surgical group to assess the outcome of surgery in 3 manometric achalasia subtypes: patients with panesophageal pressurization have the best outcome after laparoscopic Heller–Dor myotomy.
Pomaces obtained from three San Marzano tomato genotypes including the wild type (WT), Sun Black (SB), and colorless fruit epidermis (CL) were dried at 50 °C and analyzed for nutritional composition, ...total polyphenol (TPC), flavonoid (TFC) content, polyphenol qualitative profile, total antioxidant capacity (TAC), and antimicrobial activity. Commercial dried tomato powder (CTRP) was included as a control. No differences were detected nutritionally, in TPC and antimicrobial activity, but significant changes were observed for TFC and TAC, underlying variation in the phenolic profile. SB pomace (SBP) had the highest TFC and TAC. LC-HRMS analysis showed a flavonoid-enriched profile in SBP besides the exclusive presence of anthocyanins, with petanin and negretein as the most abundant. Among flavonoids, quercetin-hexose-deoxyhexose-pentose, naringenin, and rutin were the major. Overall, we showed the potential of dried tomato pomace, especially SBP, as an extremely valuable waste product to be transformed into a functional ingredient, reducing the food industry waste.
•Pomaces were obtained from wild type, Sun Black and colorless San Marzano varieties.•Pomaces were compared with commercial whole tomato powder, as control.•Experimental pomaces had a higher antioxidant capacity than the control.•Sun Black pomace had the highest flavonoids relative content: rutin was the major.•Sun Black pomace exclusively had the anthocyanins petain and negretein.
Background Transthoracic echocardiography (TTE) has been traditionally considered inadequate for the diagnosis of acute type A aortic syndrome (AAAS). In the last decade, high-resolution probes and ...harmonic imaging have been implemented in new echocardiographic systems. However, studies assessing the diagnostic accuracy of TTE for the identification of AAAS in large populations using modern ultrasound technology are lacking. Methods The diagnostic value of harmonic imaging TTE was assessed in 270 consecutive patients with suspected AAAS in whom TTE was the initial diagnostic test. Results Acute type A aortic syndrome was diagnosed in 67 patients and excluded in 203 patients (disease prevalence 25%). Sixty-two patients had a classic acute type A aortic dissection, and 5, an acute type A intramural hematoma. Image quality achieved was considered optimal in 244 patients (90%). In the whole study population, TTE had sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of AAAS of 87%, 91%, 75%, and 95%, respectively. When evaluating only patients with optimal image quality, these values increased to 97%, 100%, 100%, and 99%, respectively. Forty-seven patients with clear-cut evidence of AAAS were transferred immediately to the operative room, where transesophageal echocardiography confirmed the diagnosis obtained by TTE in all patients. Conclusions Transthoracic echocardiography is a useful imaging modality for the diagnosis of classic acute type A aortic dissection. It cannot be used as the sole screening technique for detecting AAAS, but in the light of the predictive values observed, patients with optimal image quality and clear-cut diagnosis of AAAS should proceed to the operative room, whereas in patients with negative or indeterminate studies, other imaging techniques are needed to refine the diagnosis.
Much effort has been made to explore how patients with advanced chronic illness and their families experience care when they attend the Emergency Department, and many studies have investigated how ...healthcare professionals perceive Palliative Care provision in the Emergency Department. Various models exist, but nonetheless incorporating palliative care into the Emergency Department remains challenging. Considering both healthcare professionals' and users' perspective on problems encountered in delivering and receiving appropriate palliative care within this context may provide important insight into meaningful targets for improvements in quality of care. Accordingly, this study aims at exploring issues in delivering palliative care in the Emergency Department from the perspective of both providers and users, as part of a larger project on the development and implementation of a quality improvement program in Italian Emergency Departments.
A qualitative study involving focus group interviews with Emergency Department professionals and semi-structured interviews with patients with palliative care needs in the Emergency Department and their relatives was conducted. Both datasets were analyzed using Thematic Analysis.
Twenty-one healthcare professionals, 6 patients and 5 relatives participated in this study. Five themes were identified: 1) shared priorities in Emergency Department among healthcare professionals and patients, 2) the information provided by healthcare professionals and that desired by relatives, 3) perception of environment and time, 4) limitations and barriers to the continuity of care, and 5) the contrasting interpretations of giving and receiving palliative care.
This study provides insights into targets for changes in Italian Emergency Departments. Room for improvement relates to training for healthcare professionals on palliative care, the development of a shared care pathway for patients with palliative care needs, and the optimization of Emergency Department environment. These targets will be the basis for the development of a quality improvement program in Italian Emergency Departments.
Objective To evaluate the effect of varicocelectomy on sperm retrieval at testicular sperm extraction (TESE) and at spermiograms in patients with nonobstructive azoospermia. Materials and Methods An ...observational study was conducted from April 2008 to December 2011. The study included men with a clinical diagnosis of nonobstructive azoospermia with a history of clinical unilateral varicocele (only grade III). After providing consent, the patients were treated with 2 different strategies according to the timing of varicocelectomy: group 1, varicocelectomy before microsurgical TESE (3 months); and group 2, varicocelectomy during microsurgical TESE. At 6 months after varicocelectomy, we evaluated the semen analysis findings for all patients. All patients underwent subinguinal microsurgical varicocelectomy. We also evaluated the percentage of sperm retrieval during TESE. Results During the study period, 35 patients were enrolled. Group 1 included 19 patients and group 2, 16 patients. The sperm retrieval rate during the spermiograms was significantly greater in group 1 (57.8%) than in group 2 (37.5%). The percentage of sperm retrieval during TESE between the 2 groups was significantly greater in group 1 (57.8%) than in group 2 (27%; P <.05). Conclusion Our results have suggested that varicocele repair significantly increases the sperm retrieval rate in patients with clinical varicocele and nonobstructive azoospermia at both TESE and spermiogram.
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