Peroneal mononeuropathy and polyneuropathy in adolescents with Anorexia Nervosa: a case report and literature review.

Peroneal neuropathy and polyneuropathy are displayed with a variable percentage in subjects affected by eating disorders and in particular by anorexia nervosa. Actually, little is known on features of these complications during the paediatric age. We describe the case of a female adolescent with right peroneal palsy and subclinical polyneuropathy associated with anorexia nervosa (AN). We review previous research about peroneal mononeuropathy and polyneuropathy associated with AN, and we develop a diagnostic and therapeutic protocol to help clinicians recognize and treat these disorders.

Neuroinflammation and status epilepticus: a narrative review unraveling a complex interplay.

Status epilepticus (SE) is a medical emergency resulting from the failure of the mechanisms involved in seizure termination or from the initiation of pathways involved in abnormally prolonged seizures, potentially leading to long-term consequences, including neuronal death and impaired neuronal networks. It can eventually evolve to refractory status epilepticus (RSE), in which the administration of a benzodiazepine and another anti-seizure medications (ASMs) had been ineffective, and super-refractory status epilepticus (SRSE), which persists for more than 24 h after the administration of general anesthesia. Objective of the present review is to highlight the link between inflammation and SE. Several preclinical and clinical studies have shown that neuroinflammation can contribute to seizure onset and recurrence by increasing neuronal excitability. Notably, microglia and astrocytes can promote neuroinflammation and seizure susceptibility. In fact, inflammatory mediators released by glial cells might enhance neuronal excitation and cause drug resistance and seizure recurrence. Understanding the molecular mechanisms of neuroinflammation could be crucial for improving SE treatment, wich is currently mainly addressed with benzodiazepines and eventually phenytoin, valproic acid, or levetiracetam. IL-1ß signal blockade with Anakinra has shown promising results in avoiding seizure recurrence and generalization in inflammatory refractory epilepsy. Inhibiting the IL-1ß converting enzyme (ICE)/caspase-1 is also being investigated as a possible target for managing drug-resistant epilepsies. Targeting the ATP-P2X7R signal, which activates the NLRP3 inflammasome and triggers inflammatory molecule release, is another avenue of research. Interestingly, astaxanthin has shown promise in attenuating neuroinflammation in SE by inhibiting the ATP-P2X7R signal. Furthermore, IL-6 blockade using tocilizumab has been effective in RSE and in reducing seizures in patients with febrile infection-related epilepsy syndrome (FIRES). Other potential approaches include the ketogenic diet, which may modulate pro-inflammatory cytokine production, and the use of cannabidiol (CBD), which has demonstrated antiepileptic, neuroprotective, and anti-inflammatory properties, and targeting HMGB1-TLR4 axis. Clinical experience with anti-cytokine agents such as Anakinra and Tocilizumab in SE is currently limited, although promising. Nonetheless, Etanercept and Rituximab have shown efficacy only in specific etiologies of SE, such as autoimmune encephalitis. Overall, targeting inflammatory pathways and cytokines shows potential as an innovative therapeutic option for drug-resistant epilepsies and SE, providing the chance of directly addressing its underlying mechanisms, rather than solely focusing on symptom control.

Transient ischemic attack and minor stroke as "surgeons affairs": a narrative review.

OBJECTIVE: The scope of this paper is to review the subtypes of transient ischemic attack (TIA) and minor stroke (mS) in which a surgical treatment is needed, discussing the importance and the timing of a multidisciplinary approach, in order to achieve an optimized management and prevent major strokes or other critical complications. MATERIALS AND METHODS: The keywords "transient ischemic attack," "minor stroke," "surgical treatment," "vascular surgery," "heart surgery," "neurosurgery," and "multidisciplinary" were searched using MEDLINE, EMBASE, and Scopus. Relevant search results were discussed by the authors for references inclusion. RESULTS: Notwithstanding that best medical therapy is usually the first choice for the most part of cases, there are specific but recurrent etiologies that must be properly recognized because of a potential surgical approach, even in urgency. In fact, symptomatic carotid stenosis, or particular cases of hemodynamic cerebrovascular events, should be promptly referred to vascular surgeon, since increasing evidences highlighted a benefit from an early artery revascularization. In addition, beyond arrhythmic causes, cardioembolic events due to bacterial endocarditis and atrial myxoma should be quickly diagnosed, possibly in emergency department, because they are a presumptive urgency for heart surgery. In addition to the above-mentioned conditions, in patients suffering from vertebrobasilar TIA or mS, clinicians should keep in mind the Bow Hunter disease, because surgical artery decompression can represent the only suitable treatment in selected cases. CONCLUSIONS: TIA and mS require a multidisciplinary in order to discuss therapeutic options, comparing risks and benefits and determining the best timing for an optimized management.

Berberine phospholipid exerts a positive effect on the glycemic profile of overweight subjects with impaired fasting blood glucose (IFG): a randomized double-blind placebo-controlled clinical trial.

OBJECTIVE: Berberine is a plant alkaloid known to exert positive metabolic effects. Human studies have confirmed its ability to improve the lipid and glycemic profile. This study aimed to evaluate the potential benefit of oral supplementation of Berberine PhytosomeTM (2 tablets/day, 550 mg/tablet) on the metabolic profile of subjects with impaired fasting blood glucose (IFG). PATIENTS AND METHODS: A total of 49 overweight subjects, 28 females and 21 males, were randomly assigned to either the supplemented group (n=24) or placebo (n=25). We considered glycemia as the primary endpoint and total cholesterol, high-density lipoprotein (HDL), total cholesterol/HLD, low-density lipoprotein (LDL), LDL/HDL, triglycerides, insulin, glycated hemoglobin, Homeostasis Model Assessment (HOMA), ApoA, ApoB, ApoB/ApoA, androgen suppression treatment (AST), alternative lengthening of telomeres (ALT), gamma-glutamyl transferase (GGT), creatinine, and body composition by dual-energy X-ray absorptiometry (DXA) as secondary endpoints. These parameters have been assessed at baseline, after 30 days, and after 60 days. RESULTS: After two months of treatment, through the use of linear mixed effect models, a statistically significant difference between supplemented and placebo groups was observed for glycemia [ß=-0.2495% C.I. (-0.47; -0.06), p=0.004], total cholesterol [ß=-0.25, 95% C.I. (-0.45; -0.04), p=0.05], total cholesterol/HDL [ß=-0.25, 95% C.I. (-0.43; -0.06), p=0.04], triglycerides [ß=-0.14, 95% C.I. (-0.25; -0.02), p=0.05], insulin [ß=-1.78, 95% C.I. (-2.87; -0.66), p=0.009], ApoB/ApoA [ß=-0.08, 95% C.I. (-0.13; -03), p=0.004], Visceral adipose tissue (VAT) [ß=-91.50, 95% C.I. (-132.60; -48.19), p<0.0001] and fat mass [ß=-945.56, 95% C.I. (-1,424.42; -441.57), p=0.004]. CONCLUSIONS: The use of berberine had no adverse events, supporting its use as a natural alternative to pharmacological therapies in the case of IFG.

Administration of Samital® in children with oral mucositis: a feasibility study.

OBJECTIVE: SAMITAL®, a botanical drug containing three highly standardized extracts (Vaccinium myrtillus, Macleaya cordata and Echinacea angustifolia), has shown promising results in treating or preventing oral mucositis (OM) in adult patients, but it has not been fully investigated in children. In this study, we assessed the feasibility of SAMITAL administration in pediatric patients receiving anticancer treatment to prevent or treat OM, focusing on identifying an appropriate dose and evaluating safety and tolerability and palatability and treatment compliance. PATIENTS AND METHODS: We conducted an open-label, monocentric, prospective study on 18 children receiving anticancer therapy to prevent or treat OM. RESULTS: No SAMITAL®-related side effects were observed or reported during the study; moreover, no systemic absorption of SAMITAL® metabolites was detected in the bloodstream. However, compliance to SAMITAL® was unsatisfactory and variable (from 2 to 100%), and patients reported low palatability (median taste of 4.8; range 1.0-8.0). CONCLUSIONS: SAMITAL® administration appears to be safe in the pediatric population, as it is not absorbed in the bloodstream and does not cause any local or systemic side effects. However, the current formulation is only partially suitable for children, and future studies on SAMITAL® in children would need an adapted formulation to increase compliance.

Colchicine anti-inflammatory therapy for non-intensive care unit hospitalized COVID-19 patients: results from a pilot open-label, randomized controlled clinical trial.

Systemic inflammation is a hallmark of severe coronavirus disease-19 (COVID-19). Anti-inflammatory therapy is considered crucial to modulate the hyperinflammatory response (cytokine storm) in hospitalized COVID-19 patients. There is currently no specific, conclusively proven, cost-efficient, and worldwide available anti-inflammatory therapy available to treat COVID-19 patients with cytokine storm. The present study aimed to investigate the treatment benefit of oral colchicine for hospitalized COVID-19 patients with suspected cytokine storm. Colchicine is an approved drug and possesses multiple anti-inflammatory mechanisms. This was a pilot, open-label randomized controlled clinical trial comparing standard of care (SOC) plus oral colchicine (colchicine arm) vs. SOC alone (control arm) in non-ICU hospitalized COVID-19 patients with suspected cytokine storm. Colchicine treatment was initiated within first 48 hours of admission delivered at 1.5 mg loading dose, followed by 0.5 mg b.i.d. for next 6 days and 0.5 mg q.d. for the second week. A total of 96 patients were randomly allocated to the colchicine (n=48) and control groups (n=48). Both colchicine and control group patients experienced similar clinical outcomes by day 14 of hospitalization. Treatment outcome by day 14 in colchicine vs control arm: recovered and discharged alive: 36 (75.0%) vs. 37 (77.1%), remain admitted after 14-days: 4 (8.3%) vs. 5 (10.4%), ICU transferred: 4 (8.3%) vs. 3 (6.3%), and mortality: 4 (8.3%) vs. 3 (6.3%). The speed of improvement of COVID-19 acute symptoms including shortness of breath, fever, cough, the need of supplementary oxygen, and oxygen saturation level, was almost identical in the two groups. Length of hospitalization was on average 1.5 day shorter in the colchicine group. There was no evidence for a difference between the two groups in the follow-up serum levels of inflammatory biomarkers including C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, interleukin-6 (IL-6), high-sensitivity troponin T (hs-TnT) and N-terminal pro b-type natriuretic peptide (NT pro-BNP). According to the results of our study, oral colchicine does not appear to show clinical benefits in non-ICU hospitalized COVID-19 patients with suspected cytokine storm. It is possible that the anti-inflammatory pathways of colchicine are not crucially involved in the pathogenesis of COVID-19.

An overview on the correlation between blood zinc, zinc intake, zinc supplementation and bone mineral density in humans.

INTRODUCTION: In case of zinc (Zn) deficiency, this mineral becomes a nutrient limiting muscle and bone synthesis. The study in humans on zinc and bone health are few and no reviews have been published on this topic. So, the aim of this narrative review was to consider the state of the art on the correlation between blood zinc, daily zinc intake, zinc supplementation and bone mineral density. MATERIAL AND METHODS: A narrative review was performed. RESULTS: This review included 16 eligible studies: eight studies concern Zn blood; three studies concern Zn intake and five studies concern Zn supplementation. CONCLUSION: Blood zinc levels seem to be lower in subjects with pathology related to bone metabolism. Regarding daily zinc intake, a high proportion of the population, more than 20%, seems to be at risk of having inadequate zinc intake. The literature suggests that an insufficient zinc intake (less than 3 mg/day) could be a risk factor for fractures and for development of osteopenia and osteoporosis. Zinc supplementation (40-50 g/day) could have beneficial effects on bone health in terms of maintaining bone mineral density and faster healing in the event of fractures, with even better results in situations of reduced intake zinc through food.

INTRODUCCIÓN: En caso de deficiencia de zinc, se limitará la síntesis muscular y ósea. Los estudios en humanos sobre zinc y salud ósea son pocos y no se han publicado comentarios sobre este tema. Por lo tanto, el objetivo de esta revisión narrativa es considerar el estado de la técnica sobre la correlación entre el zinc en la sangre, la ingesta diaria de zinc, la suplementación de zinc y la densidad mineral ósea. MATERIAL Y MÉTODOS: Se realizó una revisión narrativa. RESULTADOS: Esta revisión incluyó 16 estudios elegibles: ocho se refieren al zinc en sangre; tres estudios se refieren a la ingesta de Zn y cinco estudios se refieren a la suplementación de Zn. CONCLUSIÓN: Los niveles de zinc en sangre parecen ser más bajos en sujetos con patología relacionada con el metabolismo óseo. En cuanto a la ingesta diaria de zinc, una alta proporción de la población, más de 20%, parece estar en riesgo de tener una ingesta inadecuada de zinc. La literatura sugiere que una ingesta insuficiente de zinc (menos de 3 mg/día) podría ser un factor de riesgo de fracturas y para el desarrollo de osteopenia y osteoporosis. La suplementación con zinc (40-50 g/día) podría tener efectos beneficiosos sobre la salud ósea para mantener la densidad mineral ósea y una curación más rápida en caso de fracturas, con resultados aún mejores en situaciones de reducción de la ingesta de zinc a través de los alimentos.

An overview on the correlation between blood zinc, zinc intake, zinc supplementation and bone mineral density in humans / Una visión general sobre la correlación entre el zinc en la sangre, la ingesta de zinc, la suplementación de zinc y la densidad mineral ósea en los seres humanos

Abstract: Introduction: In case of zinc (Zn) deficiency, this mineral becomes a nutrient limiting muscle and bone synthesis. The study in humans on zinc and bone health are few and no reviews have been published on this topic. So, the aim of this narrative review was to consider the state of the art on the correlation between blood zinc, daily zinc intake, zinc supplementation and bone mineral density. Material and methods: A narrative review was performed. Results: This review included 16 eligible studies: eight studies concern Zn blood; three studies concern Zn intake and five studies concern Zn supplementation. Conclusion: Blood zinc levels seem to be lower in subjects with pathology related to bone metabolism. Regarding daily zinc intake, a high proportion of the population, more than 20%, seems to be at risk of having inadequate zinc intake. The literature suggests that an insufficient zinc intake (less than 3 mg/day) could be a risk factor for fractures and for development of osteopenia and osteoporosis. Zinc supplementation (40-50 g/day) could have beneficial effects on bone health in terms of maintaining bone mineral density and faster healing in the event of fractures, with even better results in situations of reduced intake zinc through food.

Resumen: Introducción: En caso de deficiencia de zinc, se limitará la síntesis muscular y ósea. Los estudios en humanos sobre zinc y salud ósea son pocos y no se han publicado comentarios sobre este tema. Por lo tanto, el objetivo de esta revisión narrativa es considerar el estado de la técnica sobre la correlación entre el zinc en la sangre, la ingesta diaria de zinc, la suplementación de zinc y la densidad mineral ósea. Material y métodos: Se realizó una revisión narrativa. Resultados: Esta revisión incluyó 16 estudios elegibles: ocho se refieren al zinc en sangre; tres estudios se refieren a la ingesta de Zn y cinco estudios se refieren a la suplementación de Zn. Conclusión: Los niveles de zinc en sangre parecen ser más bajos en sujetos con patología relacionada con el metabolismo óseo. En cuanto a la ingesta diaria de zinc, una alta proporción de la población, más de 20%, parece estar en riesgo de tener una ingesta inadecuada de zinc. La literatura sugiere que una ingesta insuficiente de zinc (menos de 3 mg/día) podría ser un factor de riesgo de fracturas y para el desarrollo de osteopenia y osteoporosis. La suplementación con zinc (40-50 g/día) podría tener efectos beneficiosos sobre la salud ósea para mantener la densidad mineral ósea y una curación más rápida en caso de fracturas, con resultados aún mejores en situaciones de reducción de la ingesta de zinc a través de los alimentos.

Hyaluronic acid in vulvar and vaginal administration: evidence from a literature systematic review.

Vulvovaginal pathology impairs the quality of life of both women in menopause and those who are not. Different therapies have been proposed, mainly related to estrogen therapy in postmenopausal women. However, some contraindications limit its use, and different moisturizers or lubricants have been tested. Hyaluronic acid is a promising and widely used vaginal medical treatment with a moisturizing action and appears to provide a solution. For this reason, we performed a systematic review of the literature. We searched for original articles without date restriction until 30 April 2020. We included all clinical trials which administered local hyaluronic acid in the vulva or vagina. Only English studies and those performed in humans were eligible. Seventeen original studies were included in the review (from randomized controlled trials to longitudinal studies). Hyaluronic acid was generally found to be effective in improving vulvovaginal symptoms (dyspareunia, itching, burning, dryness) and signs (bleeding, atrophy, vaginal pH). In conclusion, hyaluronic acid has the properties to be an efficient moisturizer for women suffering from vulvovaginal atrophy who have contraindications for estrogen therapy and for vulvovaginal signs and symptoms affecting sexual well-being. However, a well-designed randomized controlled trial is needed in order to clarify its efficacy and safety profile.

Analysis of canine myeloid-derived suppressor cells (MDSCs) utilizing fluorescence-activated cell sorting, RNA protection mediums to yield quality RNA for single-cell RNA sequencing.

Fluorescence-activated cell sorting (FACS) is a branch of flow cytometry that allows for the isolation of specific cell populations that can then be further analyzed by single-cell RNA sequencing (scRNA-seq). When utilizing FACS for population isolation prior to sequencing, it is essential to consider the protection of RNA from RNase activity, environmental conditions, and the sorting efficiency to ensure optimum sample quality. This study aimed to optimize a previously published MDSC flow cytometry strategy to FACS sort canine Myeloid-Derived Suppressor Cells (MDSC) with various permutations of RNAlater ™ and RiboLock™ before and after FACS sorting. Concentrations of RNAlater™ greater than 2 % applied before flow analysis affected cell survival and fluorescence, whereas concentrations ≤ 2 % and time ≤ 4 h had little to no effect on cells. To shorten the procedural time and to enhance the sorting of rare populations, we used a primary PE-conjugated CD11b antibody and magnetic column. The combination of RiboLock™ pre- and post-sorting for FACS provided the best quality RNA as determined by the RNA integrity number (RIN ≥ 7) for scRNA-seq in a normal and dog and a dog with untreated oral melanoma dog. As proof of principle, we sequenced two samples, one from a normal dog another from a dog with untreated oral melanoma. Applying scRNA-Seq analysis using the 10X Genomic platform, we identified 6 clusters in the Seurat paired analysis of MDSC sorted samples. Two clusters, with the majority of the cells coming from the melanoma sample, had genes that were upregulated (> log2); these included MMP9, MMP1, HPGD, CPA3, and GATA3 and CYBB, CSTB, COX2, ATP6, and COX 17 for cluster 5 and 6 respectively. All genes have known associations with MDSCs. Further characterization using pathway analysis tools was not attempted due to the lower number of cells sequenced in the normal sample. The benefit deriving from the results of the study helped to gain data consistency when working with cells prone to RNase activity, and the scRNA-seq provided data showing transcriptional heterogeneity in MDSC populations and potentially identifying previously unreported or rare cell populations.

Polycystic ovary syndrome management: a review of the possible amazing role of berberine.

PURPOSE: The therapy of polycystic ovary syndrome (PCOS) is based on synthetic hormones associated with lifestyle changes, but these therapies cannot be taken continuously, especially by women who would like to become pregnant. Thus, nutraceutical compounds were investigated as possible agents for treatment of PCOS. Berberine is shown to be effective against insulin resistance and obesity, particularly against visceral adipose tissue (VAT). Because of these properties, researchers theorized that berberine could be effective in PCOS treatment. METHODS: The aim of this narrative review was to assess the state of the art about the use of berberine in PCOS management. RESULTS: This review included 5 eligible studies. Despite the number of studies considered being low, the number of women studied is high (1078) and the results are interesting. Two authors find out that berberine induced a redistribution of adipose tissue, reducing VAT in the absence of weight loss and improved insulin sensitivity, quite like metformin. One author demonstrated that berberine improved the lipid pattern. Moreover, three authors demonstrated that berberine improved insulin resistance in theca cells with an improvement of the ovulation rate per cycle, so berberine is also effective on fertility and live birth rates. CONCLUSIONS: Finally, berberine is safe to use in premenopausal women who want to get pregnant and showed few side effects in all the cited studies. In conclusion, the use of berberine for PCOS is safe and promising, even if more studies are needed to create a consensus about the dosage of berberine useful for long-term therapy.

Siringomielia no secundaria a Chiari. Actualización en fisiopatología y manejo / Update on the pathophysiology and management of syringomyelia unrelated to Chiari malformation

Introducción: Son muchos los conocimientos y publicaciones existentes sobre la siringomielia relacionada con la malformación de Chiari, pero existe poca difusión de este cuadro cuando no se presenta en relación con dicha malformación. Ello es importante ya que es una entidad propia que precisa de un conocimiento y manejo específico. Presentamos esta revisión con el objetivo de dar a conocer las ideas más aceptadas y difundidas a día de hoy al respecto de la fisiopatología, manejo y otros aspectos de la siringomielia no secundaria a malformación de Chiari. Desarrollo: Se ha realizado una revisión de la literatura más relevante en torno a esta patología, centrándose en su fisiopatología, presentación clínica, estudio diagnóstico y manejo. Conclusiones: La siringomielia no relacionada con malformación de Chiari es una entidad propia que precisa de un conocimiento adecuado en su profundidad para su sospecha, seguimiento y manejo adecuado. Ante el hallazgo de este cuadro debe realizarse un estudio detallado encaminado a intentar identificar la causa, quedando el tratamiento sintomático como opción de rescate

Introduction: Much has been published on syringomyelia related to Chiari malformation. In contrast, little is known about the condition when it is not associated with this malformation, but this presentation of syringomyelia constitutes a different entity and therefore requires specific management. We conducted a literature review to summarise the most accepted and widespread ideas about the pathophysiology, management and other aspects of syringomyelia unrelated to Chiari malformation. Development: We reviewed the most relevant literature on this condition, focusing on the pathophysiology, clinical presentation, diagnosis, and treatment. Conclusions: Syringomyelia unrelated to Chiari malformation is a distinct entity that must be well understood to guarantee correct diagnosis, monitoring, and management. When the disease is suspected, a thorough study should be conducted to identify its aetiology. Treatment must aim to eliminate the cause of the disease; symptomatic treatment should remain a second-line option

Natural Killer Response and Lipo-Metabolic Profile in Adults with Low HDL-Cholesterol and Mild Hypercholesterolemia: Beneficial Effects of Artichoke Leaf Extract Supplementation.

The aim of the present study is to evaluate the effects of 60-day artichoke leaf extract (ALE) supplementation (250mg, twice daily) on cytokines levels, natural killer cell (NK) response, and lipo-metabolic profile (HDL, LDL, and total-cholesterol, triglycerides (TG), ApoB, ApoA, lipid accumulation product (LAP), glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR)) in twenty adults (9/11 males/females, age=49.10 ± 13.74 years, and BMI=33.12 ± 5.14 kg/m2) with low HDL-C and mild hypercholesterolemia. Hierarchical generalized linear model, adjusted for sex, BMI, and age, has been used to evaluate pre-post treatment changes. A significant increase for HDL-C (ß=0.14, p=0.0008) and MCP-1 (ß=144.77, p=0.004) and a significant decrease for ApoB/ApoA (ß=-0.07, p=0.03), total-C/HDL-C ratio (ß=-0.58, p<0.001), and NK response at stimulus low (ß=0.43, p=0.04), medium (ß=0.40, p<0.001), and high (ß=0.42, p=0.001) have been found. These results support the benefits of ALE supplementation on metabolic profile.

Update on the pathophysiology and management of syringomyelia unrelated to Chiari malformation. / Siringomielia no secundaria a Chiari. Actualización en fisiopatología y manejo.

INTRODUCTION: Much has been published on syringomyelia related to Chiari malformation. In contrast, little is known about the condition when it is not associated with this malformation, but this presentation of syringomyelia constitutes a different entity and therefore requires specific management. We conducted a literature review to summarise the most accepted and widespread ideas about the pathophysiology, management and other aspects of syringomyelia unrelated to Chiari malformation. DEVELOPMENT: We reviewed the most relevant literature on this condition, focusing on the pathophysiology, clinical presentation, diagnosis, and treatment. CONCLUSIONS: Syringomyelia unrelated to Chiari malformation is a distinct entity that must be well understood to guarantee correct diagnosis, monitoring, and management. When the disease is suspected, a thorough study should be conducted to identify its aetiology. Treatment must aim to eliminate the cause of the disease; symptomatic treatment should remain a second-line option.

Comparison between Bioimpedance Analysis and Dual-Energy X-ray Absorptiometry in assessment of body composition in a cohort of elderly patients aged 65-90 years.

We compare bioimpedance analysis (BIA) with dual-energy X-ray absorptiometry (DXA) in the assessment of free fat mass (FFM), fat mass (FM) and percentage of body fat under different conditions in relation to age categories, hydration parameters, body mass index (BMI) and sarcopenia. A cross-sectional analysis of body composition was estimated by BIA and DXA in 379 hospitalized elderly patients. In addition, estimates of FFM, FM and percentage of body fat were investigated across different conditions. Paired t-tests, Bland-Altman plot and intraclass correlation coefficient analysis were used to compare methods. Data showed an underestimation of means (BIA versus DXA) of FFM (women: 0,97 kg, p<0,01; men: 1,99 kg; p<0,01), and an overestimation of both the FM (women: +1,11 kg; p<0,01; men: +1,67 kg; p<0,01) and percentage of body fat (women: +2,07 %, p<0,01; men: +2,82 %, p<0,01). BIA underestimated FFM and overestimated FM and percentage of body fat in patients from the age group of 75 to 85 years, in patients with a total body water content <60%, in underweight and normal weight patients and in patients with sarcopenia (p<0,01). The intraclass coefficient results were indicative of poor reproducibility between BIA and DXA for FFM (women: +0,197; men: +0,250) and FM (women: +0,141; men +0,144). BIA is a good alternative for estimation of FFM and FM only in overweight or obese patients or in patients with good hydration status. BIA, on the other hand, is not an accurate method for assessing FFM in sarcopenic patients.

Apheresis treatment of cryoglobulinemic vasculitis: A multicentre cohort study of 159 patients.

OBJECTIVE: To assess the effectiveness of apheresis therapy (AT) in treating the clinical manifestations of patients with complicated cryoglobulinemic vasculitis (CV). METHODS: A retrospective cohort study of 159 CV patients attending 22 Italian Centers who underwent at least one AT session between 2005 and 2015. The response to AT was evaluated on the basis of a defined grading system. RESULTS: Peripheral neuropathy was the most frequent clinical condition leading to AT. Therapeutic plasma exchange was used in 70.4% of cases. The outcome of AT was rated very good in 19 cases, good in 64, partial/transient in 40, and absent/not assessable in 36. Life-threatening CV-related emergencies and renal impairment independently correlated with failure to respond to AT. The independent variables associated with an increased risk of death were age at the time of the first AT session, multi-organ life-threatening CV, the presence of renal impairment and failure to respond to AT. The time-dependent probability of surviving until CV-related death in the second year was 84%, with an AHR in patients with absent/not assessable response to AT of 11.25. CONCLUSION: In this study AT is confirmed to be a safe procedure in patients with CV. Early AT should be considered in patients with severe CV, especially in cases with impending renal involvement, in order to prevent irreversible kidney damage. Although its efficacy in patients with multi-organ failure is limited, AT is the only treatment that can rapidly remove circulating cryoglobulins, and should be considered an emergency treatment.

Interaction study between antiplatelet agents, anticoagulants, thyroid replacement therapy and a bioavailable formulation of curcumin (Meriva®).

OBJECTIVE: The objective of this clinical study is to evaluate possible interactions between antiplatelet agents, anticoagulants, thyroid hormone replacement therapy and a formulation of curcumin (Meriva®) that resulted effective for the complementary treatment of osteoarthritis. PATIENTS AND METHODS: Interaction between antiplatelet agents and Meriva® was evaluated by measuring anti-platelet activity with the in-vivo bleeding-time (BT) in patients assuming acetylsalicylic acid or ticlopidine or clopidogrel from at least 2 years. The BT was evaluated before and after 10 days of supplementation with Meriva®. The interaction between anticoagulants and Meriva® was evaluated in patients using warfarin or dabigatran for previous venous thrombosis. The INR level was evaluated before and after 10 days of supplementation with the curcumin formulation. Thyroid function tests in hypothyroid patients using LT4 replacement therapy (Eutirox®) were evaluated before and after 15 days of supplementation with Meriva®. Similarly, levels of glycemia and glycated hemoglobin were evaluated in diabetic patients in treatment with metformin, before and after 10 days of supplementation with the studied product. RESULTS: After 10 days of supplementation with Meriva® the average BT value was not significantly different for patients assuming acetylsalicylic acid, ticlopidine or clopidogrel at standard dosages. Similarly, after 10 days of Meriva® treatment, the INR level in the two groups of patients assuming warfarin or dabigatran was not statistically different from that observed at baseline. In the analyzed patients assuming LT4 or metformin, no interactions between the therapy and Meriva® were observed. CONCLUSIONS: Results from this non-interaction clinical study suggest that Meriva® does not interfere with the antiplatelet activity of the most common antiplatelet agents nor alters the INR values in stable patients assuming warfarin or dabigatran. Similarly, dosages of LT4 or metformin do not need to be adjusted in case of complementary treatment with Meriva®.

The increasing burden and complexity of multi-morbidity and polypharmacy in geriatric HIV patients: a cross sectional study of people aged 65 - 74 years and more than 75 years.

BACKGROUND: Geriatric Patients Living with HIV/AIDS (GEPPO) is a new prospective observational multicentre cohort consisting of all the HIV-positive geriatric patients being treated at 10 clinics in Italy, and HIV-negative controls attending a single geriatric clinic. The aim of this analysis of the GEPPO cohort was to compare prevalence and risk factors of individual non-communicable diseases (NCD), multi-morbidity (MM) and polypharmacy (PP) amongst HIV positive and HIV negative controls at enrolment into the GEPPO cohort. METHODS: This cross-sectional study was conducted between June 2015 and May 2016. The duration of HIV infection was subdivided into three intervals: < 10, 10-20 and > 20 years. The NCD diagnoses were based on guidelines defined criteria, including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease, dyslipidaemia, chronic obstructive pulmonary disease. MM was classified as the presence of two or more co-morbidities. The medications prescribed for the treatment of comorbidities were collected in both HIV positive and HIV negative group from patient files and were categorized using the Anatomical Therapeutic Chemical (ATC) classification. PP was defined as the presence of five or more drug components other than anti-retroviral agents. RESULTS: The study involved a total of 1573 patient: 1258 HIV positive and 315 HIV negative). The prevalence of individual comorbidities was similar in the two groups with the exception of dyslipidaemia, which was more frequent in the HIV-positive patients (p <  0.01). When the HIV-positive group was stratified based on the duration of HIV infection, most of the co-morbidities were significantly more frequent than in control patients, except for hypertension and cardiovascular disease, while COPD was more prevalent in the control group. MM and PP were both more prevalent in the HIV-positive group, respectively 64% and 37%. CONCLUSIONS: MM and PP burden in geriatric HIV positive patients are related to longer duration of HIV-infection rather than older age per se.

TWIST1 induces expression of discoidin domain receptor 2 to promote ovarian cancer metastasis.

The mesenchymal gene program has been shown to promote the metastatic progression of ovarian cancer; however, specific proteins induced by this program that lead to these metastatic behaviors have not been identified. Using patient derived tumor cells and established human ovarian tumor cell lines, we find that the Epithelial-to-Mesenchymal Transition inducing factor TWIST1 drives expression of discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase (RTK) that recognizes fibrillar collagen as ligand. The expression and action of DDR2 was critical for mesothelial cell clearance, invasion and migration in ovarian tumor cells. It does so, in part, by upregulating expression and activity of matrix remodeling enzymes that lead to increased cleavage of fibronectin and spreading of tumor cells. Additionally, DDR2 stabilizes SNAIL1, allowing for sustained mesenchymal phenotype. In patient derived ovarian cancer specimens, DDR2 expression correlated with enhanced invasiveness. DDR2 expression was associated with advanced stage ovarian tumors and metastases. In vivo studies demonstrated that the presence of DDR2 is critical for ovarian cancer metastasis. These findings indicate that the collagen receptor DDR2 is critical for multiple steps of ovarian cancer progression to metastasis, and thus, identifies DDR2 as a potential new target for the treatment of metastatic ovarian cancer.

A novel boswellic acids delivery form (Casperome®) in the management of musculoskeletal disorders: a review.

Standard pharmacological treatment of musculoskeletal conditions is often associated with relevant side effects. Botanical preparations endowed with a good tolerability profile, therefore, could have a role in the management of these disorders. Among different natural products, Boswellia serrata extracts have long been used for the treatment of musculoskeletal disorders, given their marked anti-inflammatory activity and their ability to promote tissue regeneration. However, standard preparations of Boswellia serrata show overall modest pharmacokinetic properties, a limitation which may ultimately lead to reduced efficacy. In an effort to improve the pharmacokinetic properties, Casperome®, a lecithin-based formulation of Boswellia serrata extract representing the whole natural bouquet, has been developed. This formulation was effective in the treatment of Achilles tendonitis, epicondylitis, radiculopathies, ankle sprains and sport injuries as shown in several clinical studies, the majority of which with a randomized design and all evaluating a number of well-recognized parameters of efficacy for the therapy of musculoskeletal disorder. All studies were consistent in showing a prompt decrease of pain and improvement of functionality of the affected area after supplementation with Casperome®, without any relevant adverse effect. Remarkably, these symptomatic improvements were paralleled by reduced plasmatic levels of inflammatory markers and by a diminished need for rescue analgesics. On these bases, Casperome® may have a role in the treatment of musculoskeletal disorders. Clinical studies in other similar conditions (e.g., osteoarthritis) appear warranted to further investigate the efficacy of this botanical product in more specific settings.