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With a prevalence of 15%, migraine is the most common neurological disorder and among the most disabling diseases, taking into account years lived with disability. Current oral medications for migraine show variable effects and are frequently associated with intolerable side effects, leading to the dissatisfaction of both patients and doctors. Injectable therapeutics, which include calcitonin gene–related peptide–targeting monoclonal antibodies and botulinum neurotoxin A (BoNT/A), provide a new paradigm for treatment of chronic migraine but are effective only in approximately 50% of subjects. Here, we investigated a novel engineered botulinum molecule with markedly reduced muscle paralyzing properties which could be beneficial for the treatment of migraine. This stapled botulinum molecule with duplicated binding domain—binary toxin-AA (BiTox/AA)—cleaves synaptosomal-associated protein 25 with a similar efficacy to BoNT/A in neurons; however, the paralyzing effect of BiTox/AA was 100 times less when compared to native BoNT/A following muscle injection. The performance of BiTox/AA was evaluated in cellular and animal models of migraine. BiTox/AA inhibited electrical nerve fiber activity in rat meningeal preparations while, in the trigeminovascular model, BiTox/AA raised electrical and mechanical stimulation thresholds in Aδ- and C-fiber nociceptors. In the rat glyceryl trinitrate (GTN) model, BiTox/AA proved effective in inhibiting GTN-induced hyperalgesia in the orofacial formalin test. We conclude that the engineered botulinum molecule provides a useful prototype for designing advanced future therapeutics for an improved efficacy in the treatment of migraine.

Background No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes. Methods Data from a national cohort study were used. We compared absolute weight gain and occurrence of excessive weight gain in women with HIV who received during pregnancy integrase inhibitors (INSTI), protease inhibitors (PI), or non-nucleoside reverse transcriptase inhibitors (NNRTI). Excessive weight gain was defined according to the Institute of Medicine recommendations. Possible predictors of weight gain were assessed using univariate and multivariate analyses. Results Among 273 cases (PI: 191, NNRTI: 43, INSTI: 39), the mean weight increase was 11.3 kg, and 25.4% of the mothers had an excessive weight increase. No significant differences were found among the three treatment groups for absolute weight increase, occurrence of excessive weight gain, infant birthweight, and other pregnancy and laboratory outcomes. The comparisons of individual drugs, although based on a limited number of cases, suggested no major differences. A significant positive correlation was found between weight gain and CD4+ T-cell increase during pregnancy. In multivariate analyses, drug class and nucleoside backbone were not associated with absolute or excessive weight increase. Excessive weight increase was significantly associated with week of delivery (adjusted odds ratio: 1.74, 95% CI 1.15, 2.63), obesity (5.21, 95% CI 1.85, 14.64), overweight (7.95, 95% CI 3.26, 19.39), recent substance use (5.96, 95% CI 1.13, 31.40) and fasting 2nd trimester hyperglycaemia (3.94, 95% CI 1.14, 13.65). Conclusions No significant differences in absolute weight change or occurrence of excessive weight gain were found among women with HIV who received during pregnancy different classes of antiretroviral drugs.

BACKGROUND The COVID-19 pandemic imposed an acute, sharp rise in the use of video consultations (VCs) by general practitioners (GPs) in Norway. OBJECTIVE This study aims to document GPs’ experiences with the large-scale uptake of VCs in the natural experiment context of the pandemic. METHODS A nationwide, cross-sectional online survey was conducted among Norwegian GPs during the pandemic lockdown (April 14-May 3, 2020). Each respondent was asked to evaluate up to 10 VCs. Basic demographic characteristics of the GPs and their practices were collected. The associations between GPs’ perceived suitability of the VCs, the nature of the patients’ main problems, prior knowledge of the patients (relational continuity), and follow-up of previously presented problems (episodic continuity) were explored using descriptive statistics, diagrams, and chi-square tests. RESULTS In total, 1237 GPs (26% of the target group) responded to the survey. Among these, 1000 GPs offered VCs, and 855 GPs evaluated a total of 3484 VCs. Most GPs who offered VCs (1000/1237; 81%) had no experience with VCs before the pandemic. Overall, 51% (1766/3476) of the evaluated VCs were considered to have similar or even better suitability to assess the main reason for contact, compared to face-to-face consultations. In the presence of relational continuity, VCs were considered equal to or better than face-to-face consultations in 57% (1011/1785) of cases, as opposed to 32% (87/274) when the patient was unknown. The suitability rate for follow-up consultations (episodic continuity) was 61% (1165/1919), compared to 35% (544/1556) for new patient problems. Suitability varied considerably across clinical contact reasons. VCs were found most suitable for anxiety and life stress, depression, and administrative purposes, as well as for longstanding or complex problems that normally require multiple follow-up consultations. The GPs estimate that they will conduct about 20% of their consultations by video in a future, nonpandemic setting. CONCLUSIONS Our study of VCs performed in general practice during the pandemic lockdown indicates a clear future role for VCs in nonpandemic settings. The strong and consistent association between continuity of care and GPs’ perceptions of the suitability of VCs is a new and important finding with considerable relevance for future primary health care planning.

OBJECTIVES: Vertical transmission of HIV can be effectively controlled through antenatal screening, antiretroviral treatment and the services provided during and after childbirth for mother and newborn. In Italy, the National Health Service guarantees universal access to prenatal care for all women, including women with HIV infection. Despite this, children are diagnosed with HIV infection every year. The aim of the study was to identify missed opportunities for prevention of mother-to-child transmission of HIV. METHODS: The Italian Register for HIV Infection in Children, which was started in 1985 and involves 106 hospitals throughout the country, collects data on all new cases of HIV infection in children. For this analysis, we reviewed the database for the period 2005 to 2015. RESULTS: We found 79 HIV-1-infected children newly diagnosed after birth in Italy. Thirty-two of the mothers were Italian. During the pregnancy, only 15 of 19 women with a known HIV diagnosis were treated with antiretroviral treatment, while, of 34 women who had received an HIV diagnosis before labour began, only 23 delivered by caesarean section and 17 received intrapartum prophylaxis. In 25 mothers, HIV infection was diagnosed during pregnancy or in the peripartum period. Thirty-one newborns received antiretroviral prophylaxis and 39 received infant formula. CONCLUSIONS: We found an unacceptable number of missed opportunities to prevent mother-to-child transmission (MCTC). Eliminating HIV MTCT is a universal World Health Organization goal. Elucidating organization failures in Italy over the past decade should help to improve early diagnosis and to reach the zero transmission target in newborns.

Background Balance and trunk control are often impaired in individuals with multiple sclerosis (MS). Interventions addressing these issues are needed. Objective The objective of this study was to compare the immediate and long-term effects of a 6-week individualized, group-based, comprehensive core stability intervention (GroupCoreDIST) with standard care on balance and trunk control in individuals with MS. Design This study was a prospective, assessor-masked, randomized controlled trial. Setting The GroupCoreDIST intervention was conducted by 6 physical therapists in 6 municipalities in Norway. Standard care included the usual care for individuals with MS in the same municipalities. Assessments at all time points took place at a Norwegian hospital. Participants Eighty people with Expanded Disability Status scores of 1 to 6.5 participated in this trial. Intervention Randomized, concealed allocation was used to assign the participants to the GroupCoreDIST intervention (n = 40) or to standard care (n = 40). The GroupCoreDIST intervention was conducted with groups of 3 participants (1 group had 4 participants), for 60 minutes 3 times per week. Measurements Assessments were undertaken at baseline and at weeks 7, 18, and 30. Outcomes were measured with the Trunk Impairment Scale–Norwegian Version, Mini Balance Evaluation Systems Test, and Patient Global Impression of Change–Balance. Repeated-measures mixed models were used for statistical analysis. Results One individual missed all postintervention tests, leaving 79 participants in the intention-to-treat analysis. GroupCoreDIST produced significant between-group effects on the mean difference in the following scores at 7, 18, and 30 weeks: for Trunk Impairment Scale–Norwegian Version, 2.63 points (95% confidence interval [CI] = 1.89–3.38), 1.57 points (95% CI = 0.81–2.33), and 0.95 point (95% CI = 0.19–1.71), respectively; for Mini Balance Evaluation Systems Test, 1.91 points (95% CI = 1.07–2.76), 1.28 points (95% CI = 0.42–2.15), and 0.91 points (95% CI = 0.04–1.77), respectively; and for Patient Global Impression of Change–Balance, 1.21 points (95% CI = 1.66–0.77), 1.02 points (95% CI = 1.48–0.57), and 0.91 points (95% CI = 1.36–0.46), respectively. Limitations Groups were not matched for volume of physical therapy. Conclusions Six weeks of GroupCoreDIST improved balance and trunk control in the short and long terms compared with standard care in individuals who were ambulant and had MS. The intervention is an effective contribution to physical therapy for this population.

Ultrafiltration (UF) is used for fluid removal during and after infant cardiopulmonary bypass (CPB) surgery to reduce fluid overload. Excessive UF may have the opposite of its intended effect, resulting in acute kidney injury (AKI), oliganuria, and fluid retention.This is a single-center, retrospective review of infants treated with conventional and/or modified UF during CPB surgery. UF volume was indexed to weight. AKI was defined using serum creatinine "Kidney Disease Improving Global Outcome (KDIGO)" criteria. Fluid balance was defined according to: [Formula: see text]. Peak fluid overload was determined on postoperative day 3. Multivariable logistic regression adjusted for multiple covariates was used to explore associations with UF, AKI, and fluid overload.Five hundred thirty subjects1 year of age underwent CPB-assisted congenital heart surgery with UF. Sixty-four (12%) developed postoperative AKI. On multivariable regression, higher indexed total UF volume was associated with increased AKI risk (OR 1.11, 95% CI=1.04-1.19, p = 0.003). UF volume119.9 mL/kg did not reduce peak fluid overload. Subjects with AKI took longer to reach a negative fluid balance (2 vs. 3 days, p = 0.04). Those with more complex surgery were at highest AKI risk (STAT 3 [25-75 percentile: 3-4] in AKI group versus STAT 3 [25-75 percentile: 2-4] in non-AKI group, p = 0.05). AKI was reduced in subjects undergoing more complex surgery and treated with UF volume119.9 mL/kg.Judicious use of UF in more complex congenital cardiac surgery reduces the risk of AKI.

Preliminary evidence supports the notion that COVID-19 patients may have an increased susceptibility to develop venous thromboembolism (VTE). However, the magnitude of this association still needs to be defined. Furthermore, clinical predictors of thrombogenesis, and the relationship with the inflammatory status are currently unknown. On this basis, we conducted a retrospective, observational study on 259 consecutive COVID-19 patients admitted to an academic tertiary referral hospital in Northern Italy between March 19th and April 6th, 2020. Records of COVID-19 patients with a definite VTE event were reviewed for demographic information, co-morbidities, risk factors for VTE, laboratory tests, and anticoagulation treatment. Twenty-five cases among 259 COVID-19 patients developed VTE (9.6%), all of them having a Padua score > 4, although being under standard anticoagulation prophylaxis since hospital admission. In the VTE subcohort, we found a significant positive correlation between platelet count (PLT) and either C reactive protein (CRP) (p p = 0.0013), while a significant inverse correlation was observed between PLT and mean platelet volume (p p p = 0.002 and p = 0.005, respectively). No significant difference was found in d-dimer levels between VTE and non VTE patients, while significantly higher levels of LDH (p = 0.04) and IL-6 (p = 0.04) were observed in VTE patients in comparison to non-VTE patients. In conclusion, our findings showed a quite high prevalence of VTE in COVID-19 patients. Raised inflammatory indexes and increased serum levels of pro-inflammatory cytokines should raise the clinical suspicion of VTE.

Background Chronic heart failure (CHF) is a prevalent disease, and CHF patients are recommended to participate in cardiac rehabilitation programs. Due to frailty and rural living, many CHF patients refuse to do so. To meet these challenges, there is need of a more convenient and efficient rehabilitation system. A home-based telerehabilitation program was designed to enable CHF patients to exercise via video-conferencing in their homes, allowing two-way communication with their therapist, and for patients to exercise together. Purpose We aimed to evaluate the feasibility of a home-based telerehabilitation exercise program designed for CHF patients. Methods 67 subjects were included in a two-arm prospective randomized controlled trial if they had stable CHF, were on optimal medical therapy, and refused to participate in standard outpatient rehabilitation. All subjects participated in a 2-day “Living with heart failure” course. The intervention group (n=30) was educated in the use of a tablet computer, a video-conferencing app, and an app with exercise videos, before they received home-based telerehabilitation exercise twice a week for 3 months. Each exercise session consisted of 20 min warm-up, followed by 4x4 min high intensity intervals with 3 min active breaks, and 15 min calm down. Outcomes, measured at baseline and 3 months, included the 6-minute walk test, the Minnesota living with heart failure Questionnaire (MLHFQ), adherence, adverse events, satisfaction, and patient reported measures of safety, technical aspects, and motivational factors. Results Mean age was 68 (65.6–71.1) years (82% male). By the 6-minute walk test, the exercise group increased their walking distance with 18 m from baseline 451 m, p=0.07. No change (+0.8 m) was seen in the control group from baseline (478 m) to 3 months, but no significant difference between groups (p=0.20). We found a significant decrease in MLHFQ score for the exercise group (baseline 42.6, change −13.8, p=0.003), and for the control group (baseline 41.2, change −12.6, p=0.002), with no difference between groups (p=0.83). ≥80% fulfilled 80% of 24 exercises. One drop-out was registered, and no adverse events were reported during exercise. In total 96% (26/27) reported that they felt safe during home-based exercise via videoconferencing and 96% (24/25) reported that the intervention gave motivation to continue exercising on their own. Some minor technical issues with the videoconference software was present in 58% (15/26). Conclusion Home-based exercise training supported by real-time supervision by telemedicine was feasible, with high adherence and high level of patients' satisfaction. Telerehabilitation increased 6-minute walking distance and quality of life in CHF patients, but the changes were not statistically significant compared to controls. Despite some technical issues with the software and equipment used, the participants reported high motivation to further exercise. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Central Norway Regional Health Authority

Background Migraine can manifest with an episodic or a chronic pattern in a continuum of disease severity. Multiple factors are associated with the progression of the pattern from episodic to chronic. One of the most consistently reported factors is the overuse of medications (MO) for the acute treatment of migraine attacks. The mechanisms through which MO facilitates the transformation of episodic migraine (EM) into chronic migraine (CM) are elusive. In order to provide insights into these mechanisms, the present study aims to identify possible peripheral biomarkers associated with the two forms of migraine, and with the presence of MO. Methods We evaluated the plasma levels of calcitonin gene-related peptide (CGRP) and the expression of miR-34a-5p and miR-382-5p in peripheral blood mononuclear cells of subjects with EM (n = 27) or CM-MO (n = 28). Subjects in the CM-MO group were also tested 2 months after an in-hospital detoxification protocol. Results CGRP, miR-382-5p, and miR-34a-5p levels were significantly higher in CM-MO subjects when compared to EM patients (p = 0.003 for all comparisons). After correcting for age, sex, and disease duration, miRNAs expression was still significantly associated with migraine phenotype (EM vs. CM-MO: p = 0.014 for miR-382-5p, p = 0.038 for miR-34a-5p), while CGRP levels were not (p = 0.115). CGRP plasma levels significantly and positively correlated with miR-382-5p (Spearman’s rho: 0.491, p = 0.001) and miR-34a-5p (Spearman’s rho: 0.303, p =0.025) in the overall population. In the CM-MO group, detoxification significantly decreased CGRP levels and miRNAs expression (p = 0.001). When comparing responders and non-responders to the detoxification, the former group (n = 23) showed significantly higher levels of CGRP at baseline, and significantly lower expression of miR-382-5p after the detoxification. Conclusions Our findings identify a potential panel of peripheral markers associated with migraine subtypes and disease severity. CGRP levels as well as miRNAs expression were influenced by MO, and modulated by detoxification in subjects with CM-MO. Trial registration The study protocol was registered at www.clinicaltrials.gov (NCT04473976).

Palmitoylethanolamide is involved in the ictal phase of episodic migraine, probably representing an analgesic and anti-inflammatory response. The endocannabinoid system is not involved in the modulation of nitroglycerin-induced central sensitization., Migraine pathophysiology has been suggested to include dysregulation of the endocannabinoid system (ES). We simultaneously evaluated plasma anandamide (AEA) and palmitoylethanolamide (PEA) levels and spinal sensitization in a validated human model of migraine based on systemic nitroglycerin (NTG) administration. Twenty-four subjects with episodic migraine (MIG) and 19 healthy controls (HC) underwent blood sampling and investigation of nociceptive withdrawal reflex thresholds (RTh: single-stimulus threshold; TST: temporal summation threshold) before and 30 (T30), 60 (T60), and 120 (T120) minutes after sublingual NTG administration (0.9 mg). At baseline, the MIG and HC groups were comparable for plasma AEA (P = 0.822) and PEA (P = 0.182) levels, and for RTh (P = 0.142) and TST values (P = 0.150). Anandamide levels increased after NTG administration (P = 0.022) in both groups, without differences between them (P = 0.779). By contrast, after NTG administration, PEA levels increased in the MIG group at T120 (P = 0.004), while remaining stable in the HC group. Nitroglycerin administration induced central sensitization in the MIG group, which was recorded as reductions in RTh (P = 0.046) at T30 and T120, and in TST (P = 0.001) at all time points. In the HC group, we observed increases in RTh (P = 0.001) and TST (P = 0.008), which suggest the occurrence of habituation. We found no significant correlations between the ES and neurophysiological parameters. Our findings suggest a role for PEA in the ictal phase of episodic migraine. The ES does not seem to be directly involved in the modulation of NTG-induced central sensitization, which suggests that the observed PEA increase and spinal sensitization are parallel, probably unrelated, phenomena.

Background Preclinical and clinical evidence suggests a role for the dysregulation of the endocannabinoid system in migraine pain, particularly in subjects with chronic migraine. Methods The gene expression of endocannabinoid system components was assayed in peripheral blood mononuclear cells of 25 subjects with episodic migraine, 26 subjects with chronic migraine with medication overuse (CM-MO) and 24 age-matched healthy controls. We also evaluated the protein expression of cannabinoid receptors 1 and 2 as well as DNA methylation changes in genes involved in endocannabinoid system components. Results Both episodic migraine and CM-MO subjects showed higher cannabinoid receptor 1 and cannabinoid receptor 2 gene and protein expression compared to controls. Fatty acid amide hydrolase gene expression, involved in anandamide degradation, was lower in migraine groups compared to healthy control subjects. N-arachidonoyl phosphatidylethanolamine phospholipase D gene expression was significantly higher in all migraineurs, as were monoacylglycerol lipase and diacylglycerol lipase gene expressions. The above markers significantly correlated with the number of migraine days and with the days of acute drug intake. Conclusion The findings point to transcriptional changes in endocannabinoid system components occurring in migraineurs. These changes were detected peripherally, which make them amenable for a wider adoption to further investigate their role and applicability in the clinical field. clinicaltrials.gov NTC04324710.

Background: Pulmonary rehabilitation is an effective treatment for people with chronic respiratory disease, but is delivered to Aims: To compare the efficacy of home-based telerehabilitation (TR) and centre-based pulmonary rehabilitation (PR) in people with chronic respiratory disease. Methods: Assessor blinded, multi-centre RCT, powered for equivalence. Participants were randomised to centre-based PR or home-based TR. Both programs were 2 sessions/week for 8 weeks. Telerehabilitation used a stationary cycle and group videoconferencing to enable social interaction and real time monitoring. The primary outcome was change in chronic respiratory disease questionnaire dyspnea domain (CRQ-D) at end rehabilitation, with a pre-specified equivalence margin of 2.5 points. Results: We randomised 142 participants to PR (n=72) or TR (n=72). Both groups had clinically important improvements in CRQ-D following rehabilitation (TR mean (95%CI) 4 (2 to 5) vs PR 5 (3 to 7)), however equivalence of TR was not confirmed (mean difference between groups (MD) -1 point (-3 to 1)), with similar findings at 12 month followup (MD -1 point (-4 to 1)). The 6-minute walk distance (6MWD) was equivalent at end rehabilitation (MD -6 metres (-26 to 15) and at 12 months superiority of TR could not be excluded (MD 14 metres (-10 to 38). The proportion of participants who completed ≥70% of prescribed sessions was high (84% TR vs 79% PR). Conclusions: Home-based TR achieved clinically important gains in health-related quality of life, but equivalence to centre-based PR was not confirmed.

Objectives To detect possible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA contamination of inanimate surfaces in areas at high risk of aerosol formation by patients with coronavirus disease 2019 (COVID-19). Methods Sampling was performed in the emergency unit and the sub-intensive care ward. SARS-CoV-2 RNA was extracted from swabbed surfaces and objects and subjected to real-time RT-PCR targeting RNA-dependent RNA polymerase and E genes. Virus isolation from positive samples was attempted in vitro on Vero E6 cells. Results Twenty-six samples were collected and only two were positive for low-level SARS-CoV-2 RNA, both collected on the external surface of continuous positive airway pressure helmets. All transport media were inoculated onto susceptible cells, but none induced a cytopathic effect on day 7 of culture. Conclusions Even though daily contact with inanimate surfaces and patient fomites in contaminated areas may be a medium of infection, our data obtained in real-life conditions suggest that it might be less extensive than hitherto recognized.

Background We evaluated the incidence of invasive pulmonary aspergillosis among intubated patients with critical COVID-19 and evaluated different case definitions of invasive aspergillosis. Methods Prospective, multicenter study in adult patients with microbiologically confirmed COVID-19 receiving mechanical ventilation. All included participants underwent a screening protocol for invasive pulmonary aspergillosis with bronchoalveolar lavage galactomannan and cultures performed on admission at 7 days and in case of clinical deterioration. Cases were classified as coronavirus-associated pulmonary aspergillosis (CAPA) according to previous consensus definitions. The new definition was compared with putative invasive pulmonary aspergillosis (PIPA). Results 108 patients were enrolled. Probable CAPA was diagnosed in 30 (27.7%) patients after a median of 4 (2–8) days from intensive care unit (ICU) admission. Kaplan-Meier curves showed a significantly higher 30-day mortality rate from ICU admission among patients with either CAPA (44% vs 19%, P = .002) or PIPA (74% vs 26%, P < .001) when compared with patients not fulfilling criteria for aspergillosis. The association between CAPA (OR, 3.53; 95% CI, 1.29–9.67; P = .014) or PIPA (OR, 11.60; 95% CI, 3.24–41.29; P < .001) with 30-day mortality from ICU admission was confirmed, even after adjustment for confounders with a logistic regression model. Among patients with CAPA receiving voriconazole treatment (13 patients; 43%) a trend toward lower mortality (46% vs 59%; P = .30) and reduction in galactomannan index in consecutive samples were observed. Conclusions We found a high incidence of CAPA among critically ill COVID-19 patients and its occurrence seems to change the natural course of disease.

Background: Subcutaneously anchored securement devices (or subcutaneous engineered securement devices) have been introduced recently into the clinical practice, but the number of published studies is still scarce. The Italian Group of Long-Term Central Venous Access Devices (GAVeCeLT)—in collaboration with WoCoVA (World Congress on Vascular Access)—has developed a Consensus about the effectiveness, safety, and cost-effectiveness of such devices. Methods: After the definition of a panel of experts, a systematic collection and review of the literature on subcutaneously anchored securement devices was performed. The panel has been divided in two working groups, one focusing on adult patients and the other on children and neonates. Results: Although the quality of evidence is generally poor, since it is based mainly on non-controlled prospective studies, the panel has concluded that subcutaneously anchored securement devices are overall effective in reducing the risk of dislodgment and they appear to be safe in all categories of patients, being associated only with rare and negligible local adverse effects; cost-effectiveness is demonstrated—or highly likely—in specific populations of patients with long-term venous access and/or at high risk of dislodgment. Conclusion: Subcutaneously anchored securement is a very promising strategy for avoiding dislodgment. Further studies are warranted, in particular for the purpose of defining (a) the best management of the anchoring device so to avoid local problems, (b) the patient populations in which it may be considered highly cost-effective and even mandatory, (c) the possible benefit in terms of reduction of other catheter-related complications such as venous thrombosis and/or infection, and—last but not least—(d) their impact on the workload and stress level of nurses taking care of the devices.

Both preclinical and clinical evidence supports the involvement of the endocannabinoid system in the pathobiology of cerebral ischemia. Selective cannabinoid-2 (CB2) receptor agonists exert significant neuroprotection in animal models of focal brain ischemia through a robust anti-inflammatory effect, involving both resident and peripheral immune cells. Nevertheless, no definitive studies demonstrating the relevance of CB2 receptors in human stroke exist. Using rtPCR and flow cytometry assays, we investigated CB2 receptor expression in circulating monocytes from 26 acute ischemic stroke patients and 16 age-matched healthy controls (CT). We also evaluated miR-665 expression, as potential CB2 receptor regulator. The median mRNA levels of CB2 were significantly (p

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder defined by multiple motor tics and at least one sound tic. Various behavioural symptoms are associated with GTS, especially obsession and compulsion behaviours (OCBs), attention-deficit/hyperactivity disorder (ADHD) and poor impulse control. These comorbid conditions have a high impact on patients quality of life, including eating attitudes and body image perception. Nutritional implications, together with sleepiness and sexual asthenia, are the principal side effects of the pharmacological therapy. Actually, drugs may compromise the nutritional status of patients producing appetite increase, dry mouth, constipation, glucose and lipid metabolism abnormalities, metabolic syndrome, mild transient dysphagia and nausea. About 40% of GTS patients experience hyperphagia because of drug side effects, OCBs, ADHD, or poor impulse control. Consequently, in these cases an overweight status can occur, complicating the management of the symptoms. Therefore, an increase body weight should be considered one of the most relevant factors increasing GTS drug-related bad compliance, which may consequently cause in some patients the discontinuation/interruption of the pharmacological therapy.

More than 10 million arterial lines are placed annually worldwide, many of which happen in the emergency department. Before the introduction of point-of-care ultrasound, landmark-guided palpation (LMGP) was considered standard of care.The objective of this study is to compare ultrasound-guided (USG) and LMGP of radial arterial line cannulation by novice emergency medicine interns.This was a single-center, prospective, randomized controlled trial (NCT03326739) of a convenience sample of adult patients who presented to an urban, university hospital with 100,000 visits annually. There was no funding for this study. Patients who required an arterial line were blindly randomized into LMGP or USG groups. Only novice emergency medicine interns, defined as interns with15 previous placements, who were not blinded, performed the cannulation. Statistical analyses included t and Fisher exact tests.Forty patients were enrolled with 20 patients randomized to each group. USG had a first-pass success of 75% vs. 0% for LMGP (p 0.00001) and an overall success of 100% vs. 15% for LMGP (p 0.00001), a mean of 1.30 attempts vs. 2.95 attempts for LMGP (a difference of 1.65; p 0.0001), and a mean time for placement of 264 s vs. 524 s for LMGP (a difference of 260; p = 0.0025). Of the failed LMGP, USG crossover was 100% successful with a mean of 1.37 attempts (95% confidence interval 0.58-2.16) and 180 s for placement (95% confidence interval 97.92-262.08). Five percent of LMGP had a complication vs. 0% for USG (p = 1.0).USG improved first-pass and overall success of radial arterial line cannulation while reducing time to access and attempts when used by novice emergency medicine interns.

The coexistence of renal and cardiac disease has been defined in dogs and cats as cardiovascular-renal disorders (CvRD). In humans, renal function is affected by recurrent episodes of acute congestive heart failure (CHF). The aim of this prospective, case-control study was to evaluate the appearance and influence of worsening cardiac disease (WCD), defined on echocardiographic and radiographic parameters, on renal function (defined as worsening renal function [WRF], on the basis of serum creatinine level and presence of proteinuria) in two population: 21 dogs with chronic mitral valve disease (CMVD) and 20 healthy dogs. Dogs were sorted into groups according to the presence/absence of WRF or WCD. Statistical analysis was performed between CMVD dogs and healthy dogs and inside the CMVD dogs group. There was no statistically significant difference in developing WRF between dogs with/without WCD and no statistical evidence to support a difference in WRF parameters in dogs experiencing CHF and dogs not experiencing it. The prevalence of azotemia in CMVD dogs was significantly higher than the prevalence of azotemia previously reported in the general population of dogs. Diuretics therapy didn’t affect renal function. No difference in survival time was seen between groups. In conclusion, CHF, WCD and diuretics therapy didn’t directly induce WRF. However, considering the prevalence of azotemia, data suggests a link between heart and kidney function (despite we didn’t excluded aged-related coexistence of organ damage). A bigger number of dogs at inclusion is required to reach statistical significance.

Both clinical features of seizures and affective problems (i.e., depressive and/or anxious symptoms) affect quality of life perception in patients with epilepsy. Although genetic generalized epilepsies (GGEs) represent one-third of all epilepsies, very few studies focused on the association among seizures, affective problems, and perceived quality of life in pediatric patients with GGE. Here, we assessed the relative contributions of seizure characteristics and affective symptoms on quality of life in patients with adolescence-onset GGE. Forty pediatric outpatients completed self-report questionnaires on affective symptoms and quality of life. Sociodemographic and clinical variables were obtained from medical charts. Affective symptoms were present in 40% of patients. Higher scores emerged in patients who were seizure-free at the time of the survey for both the physical and mental components of quality of life. Higher seizure frequency was significantly associated with lower quality of life scores in the mental component, whereas the presence of depressive and/or anxious symptoms was significantly associated with lower scores in the physical component. These associations were confirmed after controlling for sociodemographic confounders. These findings suggest that adolescents with GGE are at increased risk for affective symptoms. Moreover, both GGE-related clinical features (i.e., seizure frequency) and the presence of affective symptoms (i.e., depression, anxiety) are relevant and independent contributors to quality of life. The investigation of affective problems is warranted to be included in routine assessments of GGE in pediatric populations.

Clinical records of dogs with spontaneous degenerative mitral valve disease (DMVD) with clinical signs related to congestive heart failure (CHF) recruited during routine clinical practice between 2001 and 2018 at the Cardiology Unit of the Veterinary Teaching Hospital (University of Milan) were included in this retrospective cohort study. Baseline echocardiographic data were evaluated. Median survival time (MST) was calculated. Data on therapeutic treatment, ISACHC (International Small Animal Cardiac Health Council) or ACVIM (American College of Veterinary Internal Medicine) classes were reviewed based on the inclusion period and type of endpoint (i.e. cardiac death or death for other causes). A univocal classification was needed, and the patients classified in ISACHC classes II, IIIa and IIIb, visited before 2009, were reallocated to ACVIM class C. The main goal of this data review was to retrospectively evaluate 259 clinical records of subjects belonging to ACVIM C class examined between 2001 to 2018 and 202 dogs examined between 2010 to 2018. In this way, in the second group, the bias of the reclassification was avoided. The MST (median survival time) of these subjects was 531 d (2001-2018) and 335.5 d (2010-2018), respectively. Univariate survival regression analysis for subjects included from 2010 to 2018 showed as significantly related to cardiac death (CD): left atrium to aorta ratio (LA/Ao) (HR 2.754, p=0.000), E wave (HR 2.961, p=0.000), E/A ratio (HR 1.372, p=0.000), end-diastolic (HR 1.007, p=0.000) (EDVI) and end-systolic (HR 1.012, p=0.026) (ESVI) volume indexes, allometric diastolic (HR 4.018, p=0.000) (LVIDdN) and systolic (HR 2.674, p=0.049) (LVIDsN) left ventricular internal diameters, age (HR 1.006, p=0.009) and pulmonary hypertension severity (HR=1.309, p=0.012) (PH). Multivariate analysis, adjusted for age, showed that the only variable that determined a statistically significant difference in MST was PH severity (HR 1.334, p=0.033). The type of therapeutic treatment within this class was not significant for the MST of the subjects.

Direct acting antiviral agents (DAAs) have revolutionized the landscape of chronic hepatitis C (CHC) enabling treatment of all those infected. It remains to be determined how the characteristics of those receiving treatment are changing.We retrospectively analysed all the patients with CHC who received treatment with DAAs in a large referral centre since 01/01/2015. We stratified their demographic, clinical and virological characteristics at baseline and the sustained virological response (SVR) rates according to the year of treatment.In the study were included 2565 patients. During the study period, the yearly proportion of men and cirrhotic patients decreased (p0.001) whereas mean age increased from 59.8 to 62.2 years old (p=0.04). An increasing trend was observed in the foreign-born patients from 4.3% to 7.9%, without reaching statistical significance. The prevalence of comorbidities had also increased during the study period (p0.001). Instead, the yearly number of experienced patients decreased significantly (p0.001) as well as the mean MELD score of cirrhotic patients from 9 to 7.6 (p0.001). SVR rates increased significantly, from 93.4% in 2015 to 97.1% in 2018 (P0.05).The population of patients with CHC receiving DAAs is becoming older and with more comorbidities. Nevertheless, this did not impact SVR rates.

The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV-2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can "be protective" as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection.

In the last decade, the applicability of robotic surgery has been demonstrated in many interventions, expanding the indications of minimally invasive surgery also to pediatrics. The aim of the study is to evaluate postoperative pain to demonstrate better control following robotic procedures compared to thoraco-laparoscopic surgery. An observational, retrospective, multicentre study was performed involving 204 children undergoing robot-assisted surgery and thoraco/laparoscopic surgery at the Istituto Giannina Gaslini in Genoa and the Siena University Hospital (2013-2017): 83 children underwent robotic-assisted surgery and 121 thoracic-laparoscopic surgery. Personal data and type of intervention were assessed, dividing the patients into four categories: thoracic, gastrointestinal, hepatobiliary and urological surgeries. We analyzed the anesthetic risk according to ASA classification by type of intervention, the type of anesthesia used, the anesthetic drugs used during surgery and in the postoperative period. Both the problems that occurred during the procedures and the number of interventions converted into open during robotic surgery and laparoscopic thoracic surgery were analyzed. Pain was measured on the 1st, 2nd and 3rd day (FLACC or NRS scales). By comparing the two groups (robotics-non-robotics), the analysis shows that postoperative pain does not change with the chosen approach, but always maintains very low values, typical of minimally invasive surgery. The pain score is significantly higher in patients undergoing thoracic surgery, either robotic or thoracoscopic, compared to those undergoing gastrointestinal surgery (P corrected according to Bonferroni: 0.0006) and those undergoing urological intervention (P corrected according to Bonferroni: 0.04). In conclusion, no significant change in the intensity of postoperative pain between the two groups was found, while it is seen that the pain in patients undergoing thoracic interventions (robotic/thoracoscopic) is more intense than that reported for other types of interventions.

Background Despite the prevalence of mobile health (mHealth) technologies and observations of their impacts on patients’ health, there is still no consensus on how best to evaluate these tools for patient self-management of chronic conditions. Researchers currently do not have guidelines on which qualitative or quantitative factors to measure or how to gather these reliable data. Objective This study aimed to document the methods and both qualitative and quantitative measures used to assess mHealth apps and systems intended for use by patients for the self-management of chronic noncommunicable diseases. Methods A scoping review was performed, and PubMed, MEDLINE, Google Scholar, and ProQuest Research Library were searched for literature published in English between January 1, 2015, and January 18, 2019. Search terms included combinations of the description of the intention of the intervention (eg, self-efficacy and self-management) and description of the intervention platform (eg, mobile app and sensor). Article selection was based on whether the intervention described a patient with a chronic noncommunicable disease as the primary user of a tool or system that would always be available for self-management. The extracted data included study design, health conditions, participants, intervention type (app or system), methods used, and measured qualitative and quantitative data. Results A total of 31 studies met the eligibility criteria. Studies were classified as either those that evaluated mHealth apps (ie, single devices; n=15) or mHealth systems (ie, more than one tool; n=17), and one study evaluated both apps and systems. App interventions mainly targeted mental health conditions (including Post-Traumatic Stress Disorder), followed by diabetes and cardiovascular and heart diseases; among the 17 studies that described mHealth systems, most involved patients diagnosed with cardiovascular and heart disease, followed by diabetes, respiratory disease, mental health conditions, cancer, and multiple illnesses. The most common evaluation method was collection of usage logs (n=21), followed by standardized questionnaires (n=18) and ad-hoc questionnaires (n=13). The most common measure was app interaction (n=19), followed by usability/feasibility (n=17) and patient-reported health data via the app (n=15). Conclusions This review demonstrates that health intervention studies are taking advantage of the additional resources that mHealth technologies provide. As mHealth technologies become more prevalent, the call for evidence includes the impacts on patients’ self-efficacy and engagement, in addition to traditional measures. However, considering the unstructured data forms, diverse use, and various platforms of mHealth, it can be challenging to select the right methods and measures to evaluate mHealth technologies. The inclusion of app usage logs, patient-involved methods, and other approaches to determine the impact of mHealth is an important step forward in health intervention research. We hope that this overview will become a catalogue of the possible ways in which mHealth has been and can be integrated into research practice.