Leukocyte telomere length in women with multiple sclerosis: Comparison with healthy women during pregnancy and puerperium.

OBJECTIVES: Several studies indicated leukocyte telomere length (LTL) as a biomarker of multiple sclerosis (MS) evolution. This study aimed to investigate LTL in women with multiple sclerosis (MS) compared to that in healthy women (HW) across different reproductive phases, and to evaluate its relationship with MS activity. METHODS: Blood samples were collected from women with MS and HW during the fertile phase, pregnancy, and puerperium. LTL was determined using quantitative fluorescence in situ hybridization (Q-FISH). RESULTS: Blood samples from 68 women with MS (22 during fertile life, 23 during pregnancy, and 23 post-partum) and 52 HW (23 during fertile life, 20 during pregnancy, and 9 post-partum) were analyzed. During pregnancy, LTL in MS women and HW was 84.7 ± 10.5 and 77.6 ± 11.5, respectively (p < 0.005). Regression analysis showed that shorter LTL was associated with pregnancy in HW (p = 0.021); this relationship was not observed in MS women, for whom shorter LTL was related to a higher EDSS (p = 0.036). A longitudinal analysis was performed in eight MS women, showing LTL shortening from pregnancy to puerperium (p = 0.003), which was related to MS reactivation (p = 0.042). CONCLUSION: Our results highlight the possible associations between LTL, reproductive biological phases, and MS activity after delivery.

Evolution of teriflunomide use in multiple sclerosis: A real-world experience.

OBJECTIVES: The present study aims to describe the evolution of teriflunomide use for multiple sclerosis (MS) in the clinical setting, in particular for naïve patients and young women. Predictors of treatment response were also investigated. METHODS: This was an independent, retrospective, real-world monocentric study. We analysed the use of teriflunomide from 2016 to 2020 in patients categorized as naïve or switchers, and assessed the variations in its use in men and women by age group. Clinical and MRI data of treated patients were evaluated, and NEDA-3 status at 24 and 36 months was defined. Determinants of therapeutic response were examined using regression analysis. RESULTS: The study included 319 MS patients exposed to teriflunomide [209 women (65.5%)]. Of these, 67 (21%) were naïve and 252 (79%) were switchers. A 20% increase of teriflunomide use in the naïve group in the past two years, particularly in 2020, the first year of global Sars-Cov-2 spread, was observed. An increase of teriflunomide use of more than 10% in young women under age 45 was also reported. NEDA-3 status was calculated for 204 patients after 24 months and was achieved in 120 (58.8%) of these ones. NEDA-3 was also achieved in 92/160 (56.8%) patients at 36 months. A lower ARR in the two years prior to teriflunomide treatment (p = 0.026), lower baseline age (p = 0.05), and lower EDSS score (p = 0.009) were associated with achievement of the NEDA-3. CONCLUSIONS: Our study confirms a major evolution in teriflunomide use in clinical settings, particularly for naïve patients and young women.

The role of hepatitis B vaccine challenge dose in patients with underlying health conditions.

We have evaluated the immunological response to Hepatitis B virus (HBV) booster vaccine dose in 129 adults with underlying diseases in comparison with 694 subjects at occupational risk of infection, who have previously completed the primary series and resulted with anti-HBs <10 mIU/mL. After booster dose, 60.5% of the patients with underlying diseases and 14.8% of the subjects at occupational risk resulted seronegative. By comparing two groups, rate of subjects with anamnestic response was higher in at occupational risk group respect to that at risk for medical conditions (OR: 5.99 [95%IC, 3.81-9.41], p < .001). This difference was associated to gender (males/females: OR: 0.619 [95%IC, 0.421-0.910], p = .015) and age (better response for younger people, p = .011).

Telemedicine in pediatric wound care.

BACKGROUND: Telemedical wound care is one of the possible applications of teledermatology. The treatment of pediatric wounds needs frequent and periodic assessments of their local status and adjustment of dressings choice. MATERIALS AND METHODS: We present our experience using telemedicine in the successful assessment and treatment of 19 pediatric patients at the OPBG, Rome . Photographs with a digital camera were taken and sent weekly by mail to a wound care specialist in Rome. This allowed the expert to diagnose and evaluate the wounds periodically. RESULTS: In the shown cases, telemedicine allowed us to have an immediate evaluation and therapy adjustment. The quality of the images was good enough that the physician could regularly evaluate the status of the wound and immediately give his feedback to the parents. Of these 19, 13 patients (68%) experienced a wound resolution during the remote monitoring period. The satisfaction of the parents detected at 3, 6 and 12 months was found to be respectively 57%, 71%, 84%. CONCLUSION: Reducing transportation to the hospital to obtain a specialist advice, wound teleconsultation lowers health care costs and improve the quality of life for pediatric patients and their family, while still maintaining a high quality of pediatric wound care.

Telemedicine Home Program in Patients with Cystic Fibrosis: Results after 10 Years.

OBJECTIVES: We studied the effect of Telehomecare (THC) in a group of cystic fibrosis (CF) patients. MATERIALS AND METHODS: Forced Expiratory Volume in the first second (FEV1) was monitored at home, with the aim of an early recognition of the relapses of pulmonary infections. FEV1 was monitored for 4.5 years, using THC as a tool, in addition to the standard therapeutic protocol. 16 CF patients were followed by doctors experts in the treatment of CF, over a period of 4.5 years. We compared a control group among patients seen in the past for an identical period, matching for number, age, sex, respiratory function, bacterial colonization, O2 dependency, and complications. 16 CF patients with similar characteristics of age, degree of pulmonary involvement, bacterial colonization and O2 dependency. We calculated the annual mean values of FEV1 in both groups. RESULTS: Spirometry data showed a significant improvement in annual Fev1 mean values for the THC patients as compared to the control group. DISCUSSION: The data are encouraging for a possible role of Telemedicine as a tool for domestic assistance of patients affected by chronic diseases, such as CF. However, reliable data on the long-term effectiveness of the use of THC in the treatment of CF patients is still lacking. The time has come to obtain reliable data through a multicenter collaboration study, also in order to standardize the international Telemedicine protocols.

The application of telemedicine in the follow-up of lung transplantation in a patient with cystic fibrosis.

The Cystic Fibrosis (CF) Unit of Children's Hospital Bambino Gesù in Rome (Italy) has more than 25 years of experience in diagnosis and treatment of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) related diseases. The CF Unit actively collaborates with the Transplantation Division for the follow-up of patients with CF who undergo lung transplantation, performed in our Unit since 1991. We present the case of a 19 year-old girl with CF, with severe respiratory failure for which it was subjected to two lung transplant. During the follow-up the remote monitoring has allowed the identification of an early episode of pulmonary relapse and graft-versus-host reaction even before the onset of symptoms, allowing an effective intervention and a complete recovery of lung function.

Metabolomics network characterization of resuscitation after normocapnic hypoxia in a newborn piglet model supports the hypothesis that room air is better.

Perinatal asphyxia is attributed to hypoxia and/or ischemia around the time of birth and may lead to multiorgan dysfunction. Aim of this research article is to investigate whether different metabolomic profiles occurred according to oxygen concentration administered at resuscitation. In order to perform the experiment, forty newborn piglets were subjected to normocapnic hypoxia and reoxygenation and were randomly allocated in 4 groups resuscitated with different oxygen concentrations, 18%, 21%, 40%, and 100%, respectively. Urine metabolic profiles at baseline and at hypoxia were analysed by (1)H-NMR spectroscopy and metabolites were also identified by multivariate statistical analysis. Metabolic pathways associations were also built up by ingenuity pathway analysis (IPA). Bioinformatics analysis of metabolites characterized the effect of metabolism in the 4 groups; it showed that the 21% of oxygen is the most "physiological" and appropriate concentration to be used for resuscitation. Our data indicate that resuscitation with 21% of oxygen seems to be optimal in terms of survival, rapidity of resuscitation, and metabolic profile in the present animal model. These findings need to be confirmed with metabolomics in human and, if so, the knowledge of the perinatal asphyxia condition may significantly improve.

Program of home telemonitoring in patients with cystic fibrosis over a period of 2 years: a contribution to the rationalization of care.

OBJECTIVES: In present study we tested the possible presence of a saving for Italian National Health Service (INHS) when using telemonitoring in the follow-up at home of patients with Cystic Fibrosis (CF), in the aim to assess the possible role of Telemedicine in rationalization of hospital admissions. MATERIALS AND METHODS: We performed an economic analysis of the costs incurred by the INHS for patients with CF followed at home by telemonitoring, recalled to hospital under suspicion or diagnosis of acute pulmonary recurrence. RESULTS: We calculated, for 19 patients retrieved in the period of the study, a total saving compared to traditional home care of € 132.144,91 in 24 months, corresponding to € 3.303,62/year/patient. CONCLUSIONS: The presence of an economic advantage for the INHS is confirmed once again, although not significant. The data from this study are encouraging regarding the possible role of telemedicine in the organization of homecare of CF patients.

Evaluation of compliance to telehomecare (THC) in a group of patients with cystic fibrosis (CF) in a period of 2 years.

OBJECTIVES: In the present study, we examined data related to adherence to telemonitoring in our CF patients followed at home for a period of 2 years, in the aim to improve the follow-up in terms of efficiency and appropriateness. MATERIALS AND METHODS: We kept electronic records of transmissions, in spreadsheet format. For each transmission, the main parameters and any action taken were collected. We carried out automatically a monthly summary of activities, a monthly average percentage of adherence to prescribed frequency of transmissions, monitored the contacts and phone calls. RESULTS: We received in the period from February 15, 2010 to February 15, 2012 overall 1364 transmissions in 515 days (1817 spirometry, 414 nocturnal pulse-oximetry and 398 questionnaires on symptoms) The average compliance in the reporting period was 10,16%, with an increasing trend. CONCLUSIONS: The improvement of outcome in FC necessarily passes through an improvement of the adherence to treatment. More psychological and behavioural studies are needed in order to gradually remove the obstacles which still prevent a further improvement in long-term outcome.

Remote telematic control in cystic fibrosis.

INTRODUCTION: In this study we describe and discuss the way we daily act in remote telematic tracking of CF outpatients, a procedure which has been improved through our daily experience in telehomecare. MATERIALS AND METHODS: Currently, there are almost 30 patients involved in our telehomecare project. We describe and discuss intervention parameters and the way we manage a register of performances in spreadsheet format. We also describe the training program for the patients and their and the procedures through which we maintain contacts with patients and Vivisol assistance and the periodical satisfaction surveys. RESULTS: (from 15 of february 2010 to 24 of may 2011). Total transmissions 882, Spirometry 1317, SaO2 291, Compliance (transmissions/patient days) 8,91%, Hospital controls 19, Total contacts 722, Phone calls 494. DISCUSSION: We analyze the 2010 - 2011 data. We discuss the compliance of patients toward Telehomecare, the efficacy of cell phone in establishing contact with patients and the relevancy of symptoms' rescue in diagnosing the pulmonary relapse episodes. We discuss medico-legal aspects of telemedicine activity, in the light of standards and legislation, including issues related to the processing of privacy and security data. We discuss the professional team needs and requirements, dedicated to the activities of telemedicine and procedures related to clinical risk management. We conclude by underlying how telemedicine represents a promising new tool for patients and health professionals, and that under certain conditions it can improve the assistance, working conditions and also to reduce costs. However, its usage has to be followed by precise studies about its efficacy, and also by paying particular attention to the partly new issues that derive from it.

[Economic evaluation of telehomecare in chronic lung diseases]. / Valutazione economica del telemonitoraggio domiciliare in malattie polmonari croniche.

OBJECTIVES: We attempted to quantify the cost-effectiveness ratio in telemonitoring lung function of patients affected by Cystic Fibrosis (CF). MATERIALS AND METHODS: We examined the costs of Telehomecare (THC) in the follow-up of CF patients. We considered the failed hospitalizations as incomes. A standardized questionnaire was submitted by e-mail to verify the patient satisfaction and expectation levels. We studied 3 groups of patients: a) 17 CF patients in THC; b) 28 CF patients not followed by THC and c) 28 non-CF patients affected by chronic diseases and not followed by THC. Some parameters with no market value were evaluated using "willingness to pay" (WTP). RESULTS: An annual saving of €.5241 was calculated for single FC patient followed by THC. The WTP analysis showed that patients affected by chronic diseases expected very much from new technologies. CONCLUSIONS: The THC use in CF shows several advantages as fewer hospitalization and economical saving in a general trend of limited economical resources. Further studies are needed to confirm our data.

Five years of Telemedicine in Cystic Fibrosis Disease.

AIMS: We studied the effect of Telehomecare (THC) in a group of Cystic Fibrosis (CF) patients, with the aim to early recognize the relapses of pulmonary infections. Data obtained with Vivisol (OXYTEL) instrumentation were collected from 2001 to 2005. MATERIALS AND METHODS: The study has involved 17 patients (11 f, 6 m) affected by CF, treated with THC, in addition to the usual therapeutic protocol, for an average period of 29.6 months +/- 13.5. The mean age for THC enrollment was 15.74 years +/- 5.8. As controls, the study has involved the same patients during the 12 months prior to THC start-up and 28 patients affected by CF treated at our Unit (13 f, 15 m; average age 14.77 +/- 5.22). RESULTS: The results show a statistically significant decrease of outpatient accesses and increase of therapy cycles, and a trend of higher stability of the respiratory function, in THC treated subjects compared to controls. CONCLUSIONS: Our study suggests that THC programs may not be optimally accepted by CF patients, and that its use seems to increase in general the rate of access to health care without demonstrating any clear effect of pulmonary function.

[Attitudes toward insulin prescription in type 2 diabetic patients non-compliant with diet therapy]. / Analisi degli atteggiamenti nei confronti dell'insulina in pazienti diabetici tipo 2 non compliant alla terapia dietetica.

BACKGROUND: Investigate the compliance of type 2 diabetic patients with the prescription of insulin according to pre-existing ideas on insulin, and to personality traits. METHODS: Twenty insulin-treated type 2 diabetic patients were selected on the basis of previous scarce compliance with diet and exercise and BMI > 28 kg/m2. The patients' attitudes toward insulin prescription were evaluated with a semi-structured interview and personality traits were evaluated with the ACL test(Adjective Check List). RESULTS: When insulin was first prescribed to these patients, 65% accepted immediately. However, 45% answered that their acquiescence to insulin treatment was accompanied by doubts or apprehension. The fear of insulin dependence was shared by 50%, with a much greater prevalence among those who resisted to insulin treatment (86% vs 31%) and those who recalled doubts and fears about insulin (73% vs 22%). Patients with a fear of dependence differed significantly from the others in five personality scales: greater opposition and ambiguity, less self-confidence, more inflexible, less demanding of others and more inclined to bargain. CONCLUSIONS: The irrational fear of dependence may, therefore, play a role in both the manifest acceptance/rejection of insulin and non-expressed doubts, and may in turn be influenced by personality traits. Specific patient education on insulin treatment in type 2 diabetes is necessary, and should be planned according to the personality factors that may influence the perception of facts and the patients' motivation.

Changes in luteinizing hormone and insulin secretion in polycystic ovarian syndrome.

Uncertainties regarding the pathogenetic changes underlying the polycystic ovarian syndrome (PCOS) have been reported. The aim of this study was to investigate the endocrine and metabolic features of PCOS patients in relation to luteinizing hormone (LH) secretion. Androgen assays, oral glucose tolerance tests, hyperinsulinaemic euglycaemic clamps and gonadotrophin releasing hormone (GnRH) tests were performed in 100 patients. Sixty-six patients scheduled as hyperinsulinaemic and 34 as normoinsulinaemic showed similar concentrations of LH, follicle stimulating hormone (FSH), LH/FSH ratio, and LH response to GnRH testing. Hyperinsulinaemic subjects showed higher body mass index (BMI), insulin resistance, testosterone and free androgen index levels compared with those of normoinsulinaemic subjects; when clustered in relation to their LH basal concentrations, the two groups obtained differed only in androstenedione concentrations. Considering both insulin and LH plasma concentrations, four groups were obtained. Hyperinsulinaemia and hyper-LH secretion were not related in 54% and coexisted in the same subjects in 26% of cases. Hyperinsulinaemia as well as hyper-LH secretion affected the expression of the syndrome; the insulinaemia was directly correlated with testosterone concentrations and all metabolic parameters that affected the free androgen index. The LH concentrations were related to androgen production and were independent of BMI and insulin concentrations. It is concluded that the degree of hormonal alteration is the final sum of such pathogenetic factors.

Opioid blockade effect on insulin beta-cells secretory patterns in polycystic ovary syndrome. Oral glucose load versus intravenous glucagon bolus.

In order to evaluate the involvement of endogenous opiates in the insulin disorders of polycystic ovary syndrome (PCOs) a total of 25 PCOs women and 11 normo-ovulatory controls were studied by comparing the effect of a chronic opioid blockade on beta-cells responsiveness to oral glucose load and to intravenous glucagon bolus. Each patient, studied on follicular phase, underwent to oral glucose tolerance test (OGTT), and, 2 days later, to a glucagon intravenous bolus (1 mg); these tests were then repeated after 6 weeks of naltrexone treatment (50 mg orally). Naltrexone treatment did not modify the insulin secretory patterns of control subjects, whereas the same therapy significantly reduced, in hyperinsulinemic PCOs women, the beta-cell hyperresponsiveness both to oral glucose load and to intravenous glucagon (p < 0.05 and p < 0.01, respectively), even if with different mean percent decrease (32% OGTT vs. 45% glucagon, p < 0.05). Moreover, normoinsulinemic PCOs patients showed a slight, but not significantly increase in the beta-cells response to OGTT after opioid blockade, whereas, in the same situation, the insulin release after glucagon bolus was significantly reduced (p < 0.01). Chronic opioid blockade did not modify gonadotropins, steroids and SHBG levels in either group. Our data show that naltrexone treatment is able to reduce the beta-cell response to a direct intravenous secretagogue stimulus in all PCOs patients, while only in hyperinsulinemic PCOs subjects the same treatment is effective in reducing the exaggerated insulin secretion after oral glucose load. The reason for such a discrepancy could be ascribed to a different effect of opioids on first- and second-phase insulin secretion, or, alternatively, to an involvement of other secretagogue factors, such as glucoincretins.

Acute insulin response to intravenous glucagon in polycystic ovary syndrome.

In order to evaluate the acute insulin response after i.v. injection of glucagon in polycystic ovary syndrome (PCOS), 35 women affected by PCOS and 11 normo-ovulatory controls underwent a 75 g oral glucose tolerance test (OGTT) and, 2 days later, a glucagon test (1 mg i.v.). Patients were analysed according to their degree of obesity; the insulin release after glucagon injection for lean PCOS subjects and control women was not statistically significantly different. Conversely obese PCOS patients had higher insulin secretion after both i.v. glucagon and OGTT when compared to the other groups. Moreover the insulin secretory patterns were heterogeneously represented in lean and obese PCOS women. When the patients were analysed according to their insulinaemic response to OGTT, normoinsulinaemic PCOS women and control subjects had a similar insulin response to i.v. glucagon whereas the hyperinsulinaemic PCOS group had a higher insulin response (P < 0.0001). Moreover, a highly significant relationship was found between the insulin response to OGTT and to glucagon administration in the PCOS population (P < 0.0001; r = 0.73), which was maintained also after controlling for obesity. Our results are consistent with the hypothesis that PCOS patients could have an insulin hyper-response to glucagon administration, that is partially independent from obesity and related to their insulinaemic status. Moreover, the glucagon test could represent an effective alternative to OGTT in screening insulin disorders of PCOS patients (at least in the absence of other risk factors), due to its reliability, simplicity, and speed of performance.

Involvement of ovarian steroids in the opioid-mediated reduction of insulin secretion in hyperinsulinemic patients with polycystic ovary syndrome.

To evaluate the possible involvement of ovarian steroids on the opioid-mediated disorders of insulin in patients affected by polycystic ovary syndrome (PCOS), we studied 40 PCOS women. All patients underwent an oral glucose tolerance test (OGTT; 75 g) and basal hormone assay; based on the insulin response to OGTT, 26 women were classified as hyperinsulinemic and continued the study protocol. Patients were randomly divided into three groups characterized by different treatments: group A (nine patients) was treated with GnRH analog (one ampule every 28 days for 2 months), group B (eight patients) was treated with naltrexone (an oral opioid antagonist, 50 mg/day, orally) for 8 weeks, and group C (nine patients) was treated with GnRH analog plus naltrexone for 2 months. After continuation of treatment, all patients repeated the basal study in a second hospitalization. Naltrexone treatment significantly reduced the insulin response to OGTT, whereas GnRH analogue administration did not significantly change the insulin secretion after the glucose load. The GnRH analog/ naltrexone cotreatment was not able to influence the insulin secretory pattern; in fact, the insulin area under the curve was superimposable before and after therapy. These data could lead to the hypothesis that the opioidergic regulation of insulin secretion requires a normal steroidogenic pattern, thus suggesting that ovarian steroids modulate opioid activity also at peripheric districts.

Role of opioid tone in the pathophysiology of hyperinsulinemia and insulin resistance in polycystic ovarian disease.

Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of polycystic ovarian disease (PCOD). On the other hand, being generally admitted that opioids may play a role in glycoregulation and that opioid tone is altered in PCOD, an involvement of the opioids in determining the hyperinsulinemia of PCOD patients could be suggested. The aim of this study was to evaluate the effect of a chronic opioid blockade on insulin metabolism and peripheral insulin sensitivity in PCOD hyperinsulinemic patients. Twenty-three women with PCOD were studied. An oral glucose tolerance test (OGTT) and a clamp study were performed at baseline (during the follicular phase) and after 6 weeks of naltrexone administration (50 mg/d orally). Based on the insulinemic response to the OGTT, 16 women were classified as hyperinsulinemic and seven as normoinsulinemic. Naltrexone treatment significantly reduced fasting (P < .05) and area under the curve (AUC) (P < .02) plasma insulin levels only in the hyperinsulinemic group. Moreover, hyperinsulinemic patients showed similar C-peptide incremental areas after naltrexone treatment, whereas in the same patients the fractional hepatic insulin extraction calculated from the incremental areas of insulin and C-peptide was found to be increased after chronic opioid blockade by naltrexone. For peripheral insulin sensitivity, the hyperinsulinemic group showed significantly lower (P < .01) total-body glucose utilization (M) compared with the normoinsulinemic group. No change in the M value was found after treatment in both groups. These data suggest that the insulin sensitivity and hyperinsulinemia after an OGTT are two distinct deranged features of the insulin disorder of PCOD patients.