Towards a Deeper Understanding: Utilizing Machine Learning to Investigate the Association between Obesity and Cognitive Decline-A Systematic Review.

Background/Objectives: Several studies have shown a relation between obesity and cognitive decline, highlighting a significant global health challenge. In recent years, artificial intelligence (AI) and machine learning (ML) have been integrated into clinical practice for analyzing datasets to identify new risk factors, build predictive models, and develop personalized interventions, thereby providing useful information to healthcare professionals. This systematic review aims to evaluate the potential of AI and ML techniques in addressing the relationship between obesity, its associated health consequences, and cognitive decline. Methods: Systematic searches were performed in PubMed, Cochrane, Web of Science, Scopus, Embase, and PsycInfo databases, which yielded eight studies. After reading the full text of the selected studies and applying predefined inclusion criteria, eight studies were included based on pertinence and relevance to the topic. Results: The findings underscore the utility of AI and ML in assessing risk and predicting cognitive decline in obese patients. Furthermore, these new technology models identified key risk factors and predictive biomarkers, paving the way for tailored prevention strategies and treatment plans. Conclusions: The early detection, prevention, and personalized interventions facilitated by these technologies can significantly reduce costs and time. Future research should assess ethical considerations, data privacy, and equitable access for all.

Sexual Functioning and Sexual Health in Female Patients following Stroke: A Scoping Review with Implications for Rehabilitation.

The impact of stroke on the sexual functioning of female survivors can arise from direct neurological effects or be triggered indirectly through various psychophysiological processes. Although an increasing number of publications exist, the topic of sexuality remains seldom discussed in the stroke literature, even though patients have expressed a need for sexual rehabilitation services. A literature review on sexual functioning in post-stroke females examining existing rehabilitation programs addressing patients' sexuality and exploring the perspectives of nurses and caregivers on sexual issues constitutes a novel approach. Therefore, we conducted a scoping review to better investigate this hot topic. Studies were identified by searching Scopus, PubMed, Web of Science, Cochrane Library, PsychINFO, and Embase databases. Current data indicates substantial connections between stroke and female sexual dysfunction (SD), including factors like desire/libido, sexual satisfaction, and sexual intercourse. Some intervention programs have been created to provide specific guidance to healthcare professionals in addressing patients' requirements for sexual recovery, although their adequacy remains uncertain. However, to date, there are neither specific rehabilitation programs for post-stroke female SD nor healthcare personnel trained to deal with post-stroke sexual issues adequately and efficiently. The incorporation of sexual rehabilitation into the overall rehabilitation process for stroke patients is crucial, ideally within an interdisciplinary framework. Despite being a fundamental aspect of post-stroke women's lives, sexuality remains taboo.

Applications of Artificial Intelligence in the Neuropsychological Assessment of Dementia: A Systematic Review.

In the context of advancing healthcare, the diagnosis and treatment of cognitive disorders, particularly Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD), pose significant challenges. This review explores Artificial Intelligence (AI) and Machine Learning (ML) in neuropsychological assessment for the early detection and personalized treatment of MCI and AD. The review includes 37 articles that demonstrate that AI could be an useful instrument for optimizing diagnostic procedures, predicting cognitive decline, and outperforming traditional tests. Three main categories of applications are identified: (1) combining neuropsychological assessment with clinical data, (2) optimizing existing test batteries using ML techniques, and (3) employing virtual reality and games to overcome the limitations of traditional tests. Despite advancements, the review highlights a gap in developing tools that simplify the clinician's workflow and underscores the need for explainable AI in healthcare decision making. Future studies should bridge the gap between technical performance measures and practical clinical utility to yield accurate results and facilitate clinicians' roles. The successful integration of AI/ML in predicting dementia onset could reduce global healthcare costs and benefit aging societies.

Pediatric craniopharyngiomas: magnetic resonance imaging assessment for hypothalamus-pituitary axis dysfunction and outcome prediction.

BACKGROUND: In adamantinomatous craniopharyngiomas, tumor topographical categories, cystic component volume, and magnetic resonance signal intensity may impact prognosis. OBJECTIVE: To identify magnetic resonance imaging (MRI) variables associated with pituitary-hypothalamic axis dysfunction and predictive of outcome in children with cystic adamantinomatous craniopharyngiomas. MATERIALS AND METHODS: We evaluated 40 preoperative MRIs of adamantinomatous craniopharyngiomas to classify tumor topography, volume, and signal intensity of the cystic components and peritumoral edema. Volumes and normalized signal intensity minimum values were extracted from coronal T2-weighted images (nT2min). Radiological variables were compared to pituitary-hypothalamic axis dysfunction-related clinical data and surgical outcomes. RESULTS: Adamantinomatous craniopharyngiomas were categorized into five topographic classes (12 patients, sellar-suprasellar; seven patients, pseudo-intraventricular; six patients, strict intraventricular; 14 patients, secondary intraventricular; one patient, not strict intraventricular). All cases exhibited a predominant (30 patients, 80%) or total (10 patients, 20%) cystic tumor component and displayed low nT2min percentage values compared to cerebrospinal fluid (42.3% [interquartile range 28.4-54.6%]). Significant associations between tumor topographic classes and pituitary dysfunction (P<0.001), and between peritumoral edema and hypothalamic dysfunction (P<0.001) were found. Considering extent of surgical removal and tumor relapse, volume of the cystic tumor component displayed a positive correlation (P=0.002; r=0.48; P=0.02; r=0.36), while nT2min intensity values exhibited a negative correlation (P=0.01; r= - 0.40; P=0.028; r= - 0.34). CONCLUSION: Severe hypothalamic-pituitary axis dysfunction is associated with tumors along the pituitary stalk and peritumoral edema. Tumor invasion of the third ventricle, tight adherence to the hypothalamus, larger volumes, and lower nT2min intensity of the tumor cystic component are independent predictors of extent of adamantinomatous craniopharyngioma excision and recurrence.

Small Bowel Imaging from Stepchild of Roentgenology to MR Enterography: Part I: Guidance in Performing and Observing Normal and Abnormal Imaging Findings.

MRE has become a standard imaging test for evaluating patients with small bowel pathology, but the indications, interpretation of imaging findings, methodology, and appropriate use must be standardized and widely known. Several signs of small bowel damage in inflammatory and non-inflammatory small bowel pathology include strictures, abscess, inflammatory activity, sinus tract, wall edema, fistula, mucosal lesions, and mesentery fat hypertrophy, all of which are widely and accurately explained by MRE. MRE is a non-invasive modality that accurately assesses the intra-luminal, parietal, and extra-luminal small bowel. The differential MRE appearance allows us to distinguish between different small bowel pathologies, such as neoplastic and non-neoplastic small bowel diseases. The purpose of this paper is to present the MRE technique, as well as the interpretation of imaging findings, through the approach of a rigorous stepwise methodology.

Magnetic Resonance Imaging of Primary Adult Brain Tumors: State of the Art and Future Perspectives.

MRI is undoubtedly the cornerstone of brain tumor imaging, playing a key role in all phases of patient management, starting from diagnosis, through therapy planning, to treatment response and/or recurrence assessment. Currently, neuroimaging can describe morphologic and non-morphologic (functional, hemodynamic, metabolic, cellular, microstructural, and sometimes even genetic) characteristics of brain tumors, greatly contributing to diagnosis and follow-up. Knowing the technical aspects, strength and limits of each MR technique is crucial to correctly interpret MR brain studies and to address clinicians to the best treatment strategy. This article aimed to provide an overview of neuroimaging in the assessment of adult primary brain tumors. We started from the basilar role of conventional/morphological MR sequences, then analyzed, one by one, the non-morphological techniques, and finally highlighted future perspectives, such as radiomics and artificial intelligence.

Real-Life Impact of Drug Toxicity on Dolutegravir Tolerability: Clinical Practice Data from a Multicenter Italian Cohort.

Dolutegravir (DTG) is currently one of the most used Integrase inhibitors (INI) in antiretroviral therapies (ARV) in both naïve and experienced people living with HIV (PLWHIV). We analyzed a multicenter cohort of PLWHIV, both naïve and experienced, starting an ARV including DTG. We enrolled 3775 PLWHIV: 2763 (73.2%) were males, with a median age of 50 years. During 9890.7 PYFU, we observed 930 discontinuations (9.4 per 100 PYFU). Estimated probabilities of maintaining DTG at three and five years were 75.1% and 67.2%, respectively. Treatment-naïve pts showed a lower probability of maintaining DTG at three and five years compared to treatment-experienced PLWHIV (log-rank p < 0.001). At a multivariate analysis, a longer time of virological suppression (aHR 0.994, p < 0.001) and having experienced a previous virological failure (aHR 0.788, p = 0.016) resulted protective against DTG discontinuation. Most discontinuations (84.0%) happened within the first 12 months of DTG initiation, in particular, 92.2% of discontinuations due to neuropsychiatric toxicity were observed in the first year. Our data confirm the overall good tolerability of DTG in clinical practice, with a low rate of discontinuations. CNS toxicity resulted the main reason for DTG discontinuation, with most related interruptions happening in the first year from DTG introduction.

Anti-AT1R autoantibodies and prediction of the severity of Covid-19.

The stimulation of AT1R (Angiotensin II Receptor Type 1) by Angiotensin II has, in addition to the effects on the renin-angiotensin system, also pro-inflammatory effects through stimulation of ADAM17 and subsequent production of INF-gamma and Interleukin-6. This pro-inflammatory action stimulate the cytokine storm that characterizes the most severe forms of SARS-CoV-2 infection. We studied the effect of AT1Rab on the AT1R on 74 subjects with SARS-CoV-2 infection with respiratory symptoms requiring hospitalization. We divided the patients into 2 groups: 34 with moderate and 40 with severe symptoms that required ICU admission. Hospitalized subjects showed a 50% reduction in the frequency of AT1Rab compared to healthy reference population. Of the ICU patients, 33/40 (82.5%) were AT1Rab negative and 16/33 of them (48.5%) died. All 7 patients positive for AT1Rab survived. These preliminary data seem to indicate a protective role played by AT1R autoantibodies on inflammatory activation in SARS-CoV-2 infection pathology.

PaO2/FiO2 ratio forecasts COVID-19 patients' outcome regardless of age: a cross-sectional, monocentric study.

We studied the predictive value of the PaO2/FiO2 ratio for classifying COVID-19-positive patients who will develop severe clinical outcomes. One hundred fifty patients were recruited and categorized into two distinct populations ("A" and "B"), according to the indications given by the World Health Organization. Patients belonging the population "A" presented with mild disease not requiring oxygen support, whereas population "B" presented with a severe disease needing oxygen support. The AUC curve of PaO2/FiO2 in the discovery cohort was 0.838 (95% CI 0.771-0.908). The optimal cut-off value for distinguishing population "A" from the "B" one, calculated by Youden's index, with sensitivity of 71.79% and specificity 85.25%, LR+4.866, LR-0.339, was < 274 mmHg. The AUC in the validation cohort of 170 patients overlapped the previous one, i.e., 0.826 (95% CI 0.760-0.891). PaO2/FiO2 ratio < 274 mmHg was a good predictive index test to forecast the development of a severe respiratory failure in SARS-CoV-2-infected patients. Moreover, our work highlights that PaO2/FiO2 ratio, compared to inflammatory scores (hs-CRP, NLR, PLR and LDH) indicated to be useful in clinical managements, results to be the most reliable parameter to identify patients who require closer respiratory monitoring and more aggressive supportive therapies. Clinical trial registration: Prognostic Score in COVID-19, prot. NCT04780373 https://clinicaltrials.gov/ct2/show/NCT04780373 (retrospectively registered).

Prevalence of HEV infection in acute non-ABC hepatitis and prognostic role of extrahepatic manifestations.

Background: HEV-3 and HEV-4 are emerging cause of zoonotic acute hepatitis in high-income countries. In Europe the disease is underdiagnosed but hyperendemic areas have been identified. We describe a population with acute non-ABC (n-ABC) hepatitis in Abruzzo, the Italian region with the highest seroprevalence reported. The study was included in the surveillance of acute hepatitis E by the Italian Institute of Public Health started in 2004 and implemented in 2015. Methods: Patients with n-ABC hepatitis during 2004-2018 in all Abruzzo Infectious Disease Departments were tested for HEV-IgM (Wantai®) and HEV-RNA (ORF3). Positive samples were sequenced (Beckman Coulter®) and phylogenetic tree (MEGA 6.06 software) obtained. Clinical data were retrospectively collected and an alimentary risk factors-questionnaire was administered. Categorical and quantitative variables were compared (Chi square test or Fisher test and Wilcoxon test). Results: 97 hospitalized patients were tested, most cases (91.7%) after 2015. Overall, HEV-IgM resulted positive in 36% and HEV-RNA detectable in 33.3%. All 24 sequences obtained were HEV-3, with two small groups of closely related strands. L'Aquila was the Province with higher positivity rate (44%). Retrospective clinical data were acquired in 86.5% of patients, no one having liver failure. Higher ALT-levels (1282.34 vs 893.25, p=0.0139) and extrahepatic symptoms (OR 16.69, p=0.0018) were strongly associated with HEV-IgM presence. Two small outbreaks are described. Conclusions: More than one third of n-ABC hepatitis in all Abruzzo are HEV-related. Extrahepatic symptoms correlate with HEV aetiology. Implementing surveillance is mandatory to really understand the extent of the disease.

Automated Quantitative Lung CT Improves Prognostication in Non-ICU COVID-19 Patients beyond Conventional Biomarkers of Disease.

(1) Background: COVID-19 continues to represent a worrying pandemic. Despite the high percentage of non-severe illness, a wide clinical variability is often reported in real-world practice. Accurate predictors of disease aggressiveness, however, are still lacking. The purpose of our study was to evaluate the impact of quantitative analysis of lung computed tomography (CT) on non-intensive care unit (ICU) COVID-19 patients' prognostication; (2) Methods: Our historical prospective study included fifty-five COVID-19 patients consecutively submitted to unenhanced lung CT. Primary outcomes were recorded during hospitalization, including composite ICU admission for the need of mechanical ventilation and/or death occurrence. CT examinations were retrospectively evaluated to automatically calculate differently aerated lung tissues (i.e., overinflated, well-aerated, poorly aerated, and non-aerated tissue). Scores based on the percentage of lung weight and volume were also calculated; (3) Results: Patients who reported disease progression showed lower total lung volume. Inflammatory indices correlated with indices of respiratory failure and high-density areas. Moreover, non-aerated and poorly aerated lung tissue resulted significantly higher in patients with disease progression. Notably, non-aerated lung tissue was independently associated with disease progression (HR: 1.02; p-value: 0.046). When different predictive models including clinical, laboratoristic, and CT findings were analyzed, the best predictive validity was reached by the model that included non-aerated tissue (C-index: 0.97; p-value: 0.0001); (4) Conclusions: Quantitative lung CT offers wide advantages in COVID-19 disease stratification. Non-aerated lung tissue is more likely to occur with severe inflammation status, turning out to be a strong predictor for disease aggressiveness; therefore, it should be included in the predictive model of COVID-19 patients.

Hepatitis E Outbreak in the Central Part of Italy Sustained by Multiple HEV Genotype 3 Strains, June-December 2019.

In European countries, autochthonous acute hepatitis E cases are caused by Hepatitis E Virus (HEV) genotype 3 and are usually observed as sporadic cases. In mid/late September 2019, a hepatitis E outbreak caused by HEV genotype 3 was recognized by detection of identical/highly similar HEV sequences in some hepatitis E cases from two Italian regions, Abruzzo and Lazio, with most cases from this latter region showing a link with Abruzzo. Overall, 47 cases of HEV infection were finally observed with onsets from 8 June 2019 to 6 December 2019; they represent a marked increase as compared with just a few cases in the same period of time in the past years and in the same areas. HEV sequencing was successful in 35 cases. The phylogenetic analysis of the viral sequences showed 30 of them grouped in three distinct molecular clusters, termed A, B, and C: strains in cluster A and B were of subtype 3e and strains in cluster C were of subtype 3f. No strains detected in Abruzzo in the past years clustered with the strains involved in the present outbreak. The outbreak curve showed partially overlapped temporal distribution of the three clusters. Analysis of collected epidemiological data identified pork products as the most likely source of the outbreak. Overall, the findings suggest that the outbreak might have been caused by newly and almost simultaneously introduced strains not previously circulating in this area, which are possibly harbored by pork products or live animals imported from outside Abruzzo. This possibility deserves further studies in this area in order to monitor the circulation of HEV in human cases as well as in pigs and wild boars.

Laboratory parameters related to severe disease and death in SARS-CoV-2 pneumonia: Retrospective analysis.

The clinical evolution of coronavirus disease 2019 (COVID-19) is highly variable and hospitalized patients can rapidly develop conditions requiring oxygen support, intensive care unit (ICU) or high dependency unit (HDU) care. Early identification of high-risk patients is mandatory. We retrospectively collected the medical history, symptoms, radiological, and laboratory findings of COVID-19 patients hospitalized between February and April 2020. Laboratory data were collected at the first, last, and middle times of hospitalization. We used arterial oxygen partial pressure and fractional inspired oxygen ratio (P/F) to evaluate respiratory status. Outcomes considered were death and ICU/HDU admission. We used the χ2 or Fisher's exact test to examine differences between categorical variables. Continuous variables were analyzed using the Wilcoxon matched pairs signed-ranks test and Mann-Whitney test sample test. Of 71 patients admitted, 92% had interstitial pneumonia, and 17% an unfavorable outcome. Negative predictors were age, cerebrovascular disease, obesity, and chronic obstructive pulmonary disease. Baseline P/F was strongly associated with all outcomes. Markers linked to immunological dysregulation like elevated neutrophil-to-lymphocyte ratio exhibited prognostic significance over time. A validated prognostic score comprehensive of all these conditions for early staging and management of COVID-19 patients is urgently needed. Further studies are desirable to evaluate whether laboratory tests can target early treatment in high-risk patients.

Three Cases of COVID-19 Pneumonia in Female Patients in Italy Who Had Pulmonary Fibrosis on Follow-Up Lung Computed Tomography Imaging.

BACKGROUND Since December 2019, an outbreak caused by a novel coronavirus infection (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) occurred in Wuhan, China, and it rapidly spread all over the world. The clinical spectrum of coronavirus disease 2019 (COVID-19) is wide, with acute respiratory distress syndrome (ARDS) occurring in 15% of patients affected, requiring high oxygen support. Currently, there is no clearly effective antiviral therapy. Steroids and immunomodulators are under investigation for potential activity. Little is known about middle and long-term sequelae on respiratory function. According to some authors, COVID-19 could cause pulmonary fibrosis. We report 3 cases of pulmonary fibrosis detected on follow-up computed tomography (CT) imaging in 3 female patients who recovered from COVID-19 pneumonia in Italy (L'Aquila, Abruzzo). CASE REPORT All patients were female and had no significant previous respiratory disease or history of smoke exposure, and none had received high-flow oxygen support during treatment of the disease. In all cases, late onset of mild dyspnea, slow and incomplete respiratory recovery, and early evidence of fibrous signs on chest CT scan were characteristic of the clinical course. CONCLUSIONS This report focuses on a possible scenario of long-term lung damage in COVID-19 pneumonia survivors. Limitations are lack of long-term follow-up and functional data in the very early phase. It is advantageous that all COVID-19 pneumonia patients undergo serial chest CT and spirometry long-term follow-up for at least 1 year to assess residual damage. This is particularly relevant in those with slow respiratory recovery and long hospitalization.

Phylogenetic analysis and epidemiological history of Hepatitis E virus 3f and 3c in swine and wild boar, Italy.

BACKGROUND: Hepatitis E virus (HEV) genotype 3 has a worldwide distribution. The food-borne transmission of HEV associated with the consumption of products derived from domestic pig, wild boar has been reported in various countries. In this study the genetic diversity, evolutionary rates of HEV 3f, 3c among swine and wild boar in Italy were estimated. METHODS: Sampling was performed on a wild boar population living in an area located in Abruzzo region. The HEV RNA amplification was performed by real-time RT-PCR. Nested RT-PCR and sequencing of the ORF2 region were carried out by the Super Script III First-Strand Synthesis System. Sequencing of purified PCR products was carried out by the Genome Lab Dye Terminator Cycle Sequencing (DTCS) Quick Start Kit. The maximum likelihood trees were generated by using Phyml. The mean evolutionary rates and the dated trees were co-estimated by BEAST. RESULTS: The phylogenetic analysis showed that the HEV ORF2 isolates from Abruzzo region belonged to 3f subtype. The prevalent subtypes in Italy were those belonging to 3f and 3c. The estimated mean values of the HEV ORF2 capsid gene evolutionary rates were 1.915 × 10-2 substitutions/site/year (95% HPD: 1.64 × 10-3 - 3.97 × 10-2) and 2.81 × 10-2 substitutions/site/year (1.83 × 10-2 - 3.8 × 10-2) for 3f and 3c subtype datasets, respectively.The HEV 3f dated back to 1985 (1960-2000), whereas the 3c subtype entered in Italy during the year 2006 (2005-2006). The majority of the HEV 3f sequences collected from swine didn't appear intermixed, except in two cases. The HEV 3c population circulating in Italy remained segregated without significant transfer to swine. CONCLUSION: Our study provide insight into the evolution, circulation of HEV 3f and 3c in Italy.Continued genomic surveillance of HEV in animal reservoir, as well as improving sanitary control measures are required.

Follow-up and Management of Kidney Transplant Recipients During the COVID-19 Lockdown: The Experience of an Italian Transplant Center, Including Two Cases of COVID-19 Pneumonia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new infectious disease that emerged in China in late 2019 and is now spreading around the world. Social distancing measures were needed to reduce transmission, and lockdown included restricted access to health care facilities. The impact of COVID-19 on transplant recipients is unknown, but considering their immunosuppression status and associated comorbidities, they should be considered a high-risk population. METHODS: A kidney transplant center in Central Italy implemented a strategy to maintain follow-up of kidney transplant recipients by phone and e-mail during lockdown. Telephone interviews were used to administer a clinical questionnaire to patients, and e-mail was used to receive the results of diagnostic tests conducted in outpatient settings. RESULTS: From March 17 to April 23, 2020, a total of 143 kidney transplant recipients were contacted. Twenty-eight patients needed in-hospital consultation for problems unrelated to COVID-19, 3 of whom needed hospitalization. Eleven patients were managed at home for mild urinary or respiratory diseases, and 1 was referred to the hematologist. We identified 2 suspected cases of COVID-19 infection, and the patients were referred to hospital care. Immunosuppressive therapy was modulated, and intravenous corticosteroids and potentially effective antiviral therapy were administered with a favorable outcome. CONCLUSIONS: In the context of a lockdown, such as that occurring in response to COVID-19, we suggest implementing remote surveillance programs in kidney transplant recipients with the help of any available technology and offering medical consulting and logistic support as needed.

A "One-Health" approach for diagnosis and molecular characterization of SARS-CoV-2 in Italy.

The current pandemic is caused by a novel coronavirus (CoV) called SARS-CoV-2 (species Severe acute respiratory syndrome-related coronavirus, subgenus Sarbecovirus, genus Betacoronavirus, family Coronaviridae). In Italy, up to the 2nd of April 2020, overall 139,422 confirmed cases and 17,669 deaths have been notified, while 26,491 people have recovered. Besides the overloading of hospitals, another issue to face was the capacity to perform thousands of tests per day. In this perspective, to support the National Health Care System and to minimize the impact of this rapidly spreading virus, the Italian Ministry of Health involved the Istituti Zooprofilattici Sperimentali (IZSs), Veterinary Public Health Institutes, in the diagnosis of SARS-CoV-2 by testing human samples. The Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise is currently testing more than 600 samples per day and performing whole genome sequencing from positive samples. Sequence analysis of these samples suggested that different viral variants may be circulating in Italy, and so in Abruzzo region. CoVs, and related diseases, are well known to veterinarians since decades. The experience that veterinarians operating within the Public Health system gained in the control and characterization of previous health issues of livestock and poultry including avian flu, bluetongue, foot and mouth disease, responsible for huge economic losses, is certainly of great help to minimize the impact of this global crisis.

Hepatitis E infection in a patient with rheumatoid arthritis treated with leflunomide: A case report with emphasis on geoepidemiology.

RATIONALE: Hepatitis E is an infectious disease due to inflammation of the liver caused by hepatitis E virus (HEV) and represents one of the most common causes of acute hepatitis and jaundice in the world. Although data of hepatitis E infection in patients with rheumatoid arthritis (RA) are accumulating, little is known on the course of HEV infection. We reported, for the 1st time, a case of patient with RA with hepatitis E that developed during leflunomide therapy in combination with low-dose steroids. PATIENT CONCERNS: We present a 39-year-old woman, affected by RA and treated with leflunomide, reported diffuse itching and persistent fatigue laboratory data revealed elevated liver enzyme levels. DIAGNOSIS: Positivity for anti-HEV IgM and IgG was observed. HEV-RNA of the genotype 3 was detected, indicating acute E hepatitis. INTERVENTIONS AND OUTCOMES: Leflunomide was stopped and restarted 5 months after the initial diagnosis at the same dosage, with a close clinical and laboratory follow-up. The virus was eradicated from the serum without chronic transformation. The patient is alive and well 7 months after the initial diagnosis. LESSONS: To our knowledge, this report is the 1st case of acute E hepatitis in a patient with RA developed during leflunomide therapy in combination with low-dose steroids. Moreover, geoepidemiology of infection is important, due to the fact that Abruzzo, a central region of Italy, has the highest HEV seroprevalence in general population, related to the zoonotic transmission of the infection from domestic and wild animals. Our case highlighted that immunosuppressive therapy, and in particular leflunomide, could be safely reintroduced after the resolution of the infection and the clearance of the virus. Further studies are needed to evaluate potential advantages in serologic testing for HEV infection as a part of the routine workup done to patients with rheumatic diseases and selected for immunosuppressive therapy.

The influence of physiotherapy intervention on patients with multiple sclerosis-related spasticity treated with nabiximols (THC:CBD oromucosal spray).

BACKGROUND: Nabiximols (THC/CBD Oromucosal Spray, Sativex) is used as an add-on therapy to treat moderate to severe spasticity of Multiple Sclerosis (MS). OBJECTIVES: To examine the impact of physiotherapy (PT) programs on effectiveness and persistence of nabiximols treatment in people with MS-related spasticity. METHODS: This is an observational multicenter study with a follow-up period of 12 weeks, conducted in routine care settings in Italy. Patients with moderate to severe MS-related spasticity who started nabiximols were included. Spasticity was evaluated by the patient-rated 0-10 numerical rating scale (NRS). Clinical data were collected at baseline (T0), 4 weeks (T1) and 12 weeks (T2) months after enrollment. RESULTS: A total of 297 MS patients were selected, 290 completed the 3 months follow-up period. Mean NRS scores were 7.6 ± 1.1 at T0, 5.8 ± 1.4 at T1 and 5.5 ± 1.5 at T2. At T1, 77% of patients reached ≥20% improvement (initial response, IR); 22% reached ≥30% improvement (clinically relevant response, CRR). At T1, patients undergoing PT had a higher probability to reach CRR (Odds Ratio = 2.6 95% CI 1.3-5.6, p = 0.01). Nabiximols was discontinued in 30/290 (10.3%) patients at T1 (early discontinuers) and in 71/290 (24.5%) patients at T2 (late discontinuers). The probability of being late discontinuers was reduced in patients undergoing PT (Hazard Ratio = 0.41; 95% CI 0.23-0.69, p = 0.001). CONCLUSIONS: Our real-life study confirms nabiximols' effectiveness in MS-related spasticity and suggests that the association of a PT program may improve overall response and persistence to nabiximols treatment.

Advances in preventing adverse events during monoclonal antibody management of multiple sclerosis.

INTRODUCTION: Decades of pharmacological research in Multiple Sclerosis (MS) led to the development of therapeutic Monoclonal Antibodies (MAbs) with many different mechanisms of action (MoA), potentially able to improve disability outcome but also determining a more complex management of patients. Areas covered: When clinicians select MS treatments, they should consider adverse events (AEs) on individual basis to minimize patients' risks. Some AEs are common and can be easily handled, but rare complications should also be taken into account. The aim of this review is to summarize existing evidence and provide practical recommendations for the management of therapeutic MAbs in MS. Expert opinion: The introduction of MAbs revolutionized MS treatment with an improvement in effectiveness. Unfortunately, this has been coupled with a more complex array of AEs needing a tighter surveillance strategy. A close interaction between general practitioners, neurologists, and other specialists is the key for a safer use of such effective drugs.