Acetyl-L-carnitine Slows the Progression from Prefrailty to Frailty in Older Subjects: A Randomized Interventional Clinical Trial.

BACKGROUND: Ageing is characterized by a gradual decline in body function, representing the clinical situation called "frailty". Prefrailty is the intermediate stage between frailty and robust condition. L-carnitine (LC) plays an important role in energy production from long-chain fatty acids in mitochondria, and its serum level is lower in prefrail and frail subjects. OBJECTIVE: This study aims to evaluate the effect of Acetyl-L-carnitine (ALCAR) in pre-frail older patients. METHODS: We scheduled 3 months of treatment and then 3 months of follow-up. A total of 92 subjects were selected from May, 2009 to July, 2017, in a randomized, observational, double-blind, placebo-controlled study. We scheduled 3 months of treatment and then 3 months of follow-up. ALCAR (oral 1.5 g/bis in die - BID) or placebo groups were used. RESULTS: After the treatment, only the treated group displayed a decrease in C reactive protein (CRP) p < 0.001 and an increase in serum-free carnitine and acetylcarnitine (p < 0.05) in Mini-Mental state (MMSE) p < 0.0001 and 6-walking distance (p < 0.0001); ALCAR group vs. placebo group showed a decrease in HDL cholesterol and CRP (p < 0.01), an increase in MMSE score (p < 0.001) and in the 6-walking distance (p < 0.001). CONCLUSIONS: ALCAR treatment delays the incidence and severity of onset of degenerative disorders of the elderly in prefrail subjects with improvement in memory and cognitive processes.

Serum Folate deficiency in HCV related Hepatocellular Carcinoma.

Nutritional and environmental factors had been reporting in the progression of hepatocellular carcinoma (HCC). In this study, we focused our intervention in the correlation between the folate status and the progression of HCC in patients with chronic virus C (HCV) infection. Nine-eight patients, HCV positive with HCC and one hundred of patients with HCV positive liver cirrhosis (LC) and one hundred patients with HCV positive chronic hepatitis (CHC) and one hundred control subjects were enrolled. The viremia for hepatitis C patients (HCV) was determined by HCV RNA with polymerase chain reaction. HCV was confirmed by HCV RNA or a positive anti-HCV test with chronic liver disease. The comparison of folate serum levels in HCC patients vs Liver Cirrhosis (LC) patients showed a significant decrease of 1.16 ng/ml P = 0.0006 (95% CI-1.925 to - 0.395), in HCC patients versus CHC a decrease of 1.40 ng/ml P < 0.0001 (95% CI-2.16 to - 0.63), in HCC vs controls a decrease of 3.80 ng/ml P < 0.0001 (95% CI-4.56 to - 3.03). The comparison of homocysteine Hcy serum levels showed a significant increase in HCC vs LC of 4 nmol/L (P < 0.0001, 95% CI 2.77 to 5.22) versus CHC of 9 nmol/L (P < 0.0001, 95% CI 7.78 to 10.22) and vs Controls 9.30 nmol/L (P < 0.0001, 95% CI 8.07 to 10.52). With progression of HCV infection from chronic hepatitis to cirrhosis, then to HCC development, serum folate levels are progressively decreasing together with a progressive increase in serum homocysteine levels reflecting its role in disease progress and carcinogenesis.

The translational roadmap of the gut models, focusing on gut-on-chip.

It is difficult to model in vitro the intestine when seeking to include crosstalk with the gut microbiota, immune and neuroendocrine systems. Here we present a roadmap of the current models to facilitate the choice in preclinical and translational research with a focus on gut-on-chip. These micro physiological systems (MPS) are microfluidic devices that recapitulate in vitro the physiology of the intestine. We reviewed the gut-on-chips that had been developed in academia and industries as single chip and that have three main purpose: replicate the intestinal physiology, the intestinal pathological features, and for pharmacological tests.

Carnitine Serum Levels in Frail Older Subjects.

Frailty is an expression that reconciles and condenses loss of autonomy, both physical and cognitive decline and a wide spectrum of adverse outcomes due to aging. The decrease in physical and cognitive activity is associated with altered mitochondrial function, and energy loss and consequently morbidity and mortality. In this cross-sectional study, we evaluated the carnitine levels in frailty status. The mean serum concentrations of total carnitine (TC) were lower in frail elderly subjects than in prefrail ones (p = 0.0006), higher in frail vs. robust subjects (p < 0.0001), and higher in prefrail vs. robust subjects (p < 0.0001). The mean serum concentrations of free carnitine (FC) were lower in frail elderly subjects than in prefrail ones (p < 0.0001), lower in frail vs. robust subjects (p < 0.0001) and lower in prefrail vs. robust subjects (p = 0.0009). The mean serum concentrations of acylcarnitine (AC) were higher in frail elderly subjects than in prefrail ones (p = 0.054) and were higher in pre-frail vs. robust subjects (p = 0.0022). The mean urine concentrations of TC were lower in frail elderly subjects than in prefrail ones (p < 0.05) and lower in frail vs. robust subjects (p < 0.0001). The mean urine concentrations of free carnitine were lower in frail elderly vs. robust subjects (p < 0.05). The mean urine concentrations of acyl carnitines were lower in frail elderly subjects than those in both prefrail (p < 0.0001) and robust subjects (p < 0.0001). Conclusion: high levels of carnitine may have a favorable effect on the functional status and may treat the frailty status in older subjects.

Corrigendum to "Iatrogenic nerve lesion following laparoscopic surgery. A case reportË® [Ann. Med. Surg. 28 (2018) 34-37].

[This corrects the article DOI: 10.1016/j.amsu.2018.02.002.].

Folate levels in hepatocellular carcinoma patients with portal vein thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) occurs frequently in hepatocellular carcinoma (HCC) and is often diagnosed in the course of a routine patient evaluation and surveillance for liver cancer. The purpose of this study is to investigate the relationship between folate status and portal vein thrombosis. METHODS: HCC with PVT patients were 78, HCC without PVT were 60 and control subjects were 70 randomly selected. We evaluate serum and red blood cellular folate, homocysteine, alpha fetal protein cholesterol, triglycerides, prothrombin time. RESULTS: HCC patients with PVT showed lower levels of serum folate, respect HCC patients without PVT, with an average difference of 1.6 nmol/l p < 0.01 (95% CI - 2.54 to - 0.66), red cell folate 33.6 nmol/l p < 0.001 (95% CI - 43.64 to - 23.55) and albumin 0.29 g/dl p < 0.001 (95% CI - 0.42 to - 0.15); PVT patients displayed higher levels of bilirubin 0.53 mg/dl p < 0.001 (95% CI 0.23 to 0.78), INR 0.91 p < 0.001 (95% CI 0.72 to 1.09), γGT 7.9 IU/l (95% CI 4.14 to 11.65) and homocysteine 4.6 µmol/l p < 0.05 (95% CI 0.32 to 8.87) CONCLUSION: The low folate concentration and higher levels of homocysteine are associated with the loss of antithrombotic function, and with a more aggressive course of HCC and with a higher change of complications related to portal vein thrombosis.

Hepatitis C Virus Infection Increases Fatigue in Health Care Workers.

Fatigue is a common state associated with a weakening or depletion of one's physical and mental resources, that leads to the inability to continue the individual functioning at a normal level of activity. Frequently, fatigue represents a response to infections, inflammation and autoimmune diseases. The scope of this study was to evaluate the fatigue in healthcare workers with and without hepatitis C virus (HCV) infection. Mental, physical and severity fatigue were evaluated through Krupp, Wessely and Powell fatigue scale. Anti-HCV antibodies, HCV RNA and HCV genotypes were also measured. Physical, mental and severity fatigue were higher in healthcare workers with HCV infection than the healthcare workers without infection (p < 0.01). Our data showed a direct link between fatigue and HCV infection in healthcare workers. Further studies are needed to evaluate HCV antiviral treatments on fatigue severity and on quality of life in healthcare workers.

High Carbohydrate 19-9 Antigen Serum Levels in Patients with Nonmelanoma Skin Cancer and Primary Occult Cancer.

BACKGROUND: Non-melanoma skin cancers (NMSC), despite having a favourable prognosis, present an increased risk of occult malignancies. The aim of this study was the evaluation of the usefulness of the mucinous marker carbohydrate 19-9 antigen (CA 19-9) in the diagnosis of occult cancers. (1) Patients and Methods: This is a case control study in which 480 patients with NMSC and 480 matched control subjects with dermatitis were enrolled; 208 patients with NMSC showed upper-normal CA 19-9 values, and 272 showed under-normal CA 19-9 values. (2) Results: The 208 patients positive for CA 19-9 included 87 with basal cell carcinoma (BCC) and 121 with squamous cell carcinoma (SCC). The 272 patients negative for CA 19-9 included 107 with BCC and 165 with SCC. For the SCC patients, CA 19-9 serum levels were significant in 121 of the patients (positive), 66 of which were affected by cancer; CA 19-9 was within the normal range in 165 patients, of which 30 were diagnosed with cancer. In the SCC patients, the CA 19-9 sensitivity was 68%, the specificity was 70%, the positive predictive value (PPV) was 54% (95%) and the negative predictive value (NPV) was 81%. In the BCC patients, the CA 19-9 sensitivity was 70%, the specificity was 66%, the PPV was 48% and the NPV was 83%. In the dermatitis patients (controls), we observed 121 patients that were CA 19-9 positive, with 15 malignancies, and 359 CA 19-9-negative patients, with three malignancies. (3) Conclusions: To confirm the association between CA 19-9 and an elevated risk of malignancies in NMSC, prospective cohort studies should be performed.

Dry Eye in Systemic Sclerosis Patients: Novel Methods to Monitor Disease Activity.

BACKGROUND: In systemic sclerosis (SSc) patients, dry eye syndrome (DES) is the most frequent ocular feature. The aim of this study was to investigate ocular DES-related SSc patients and to establish any correlation with the severity of the disease. METHODS: Retrospectively, data from 60 patients with SSc underwent ophthalmic examination, where non-invasive film tear break-up time (NIF-TBUT), tear film lipid layer thickness (LLT), anesthetic-free Schirmer test I, tear osmolarity measurement (TearLab System), and modified Rodnan skin score (mRSS) data were collected. The visual analog scale (VAS) and Symptom Assessment in Dry Eye (SANDE) methods were utilized. The results were correlated with mRSS and the duration of SSc. RESULTS: Severe DES occurred in 84% of cases, and was more severe in women. The eyelids were involved in 86.6%, secondary to meibomian gland disease (MGD). A direct correlation was found between the tear osmolarity (mean 328.51 ± 23.8 SD) and skin score (mRSS) (r = 0.79; p < 0.01). Significantly reduced NIF-TBUT, LLT, and Schirmer test I values were observed in the case of severe skin involvement. CONCLUSIONS: SSc patients show lipid tear dysfunction related to the severity and duration of the disease due to inflammation and the subsequent atrophy of the meibomian glands.

Acetyl-L-Carnitine in Dementia and Other Cognitive Disorders: A Critical Update.

Several studies explored the effects of acetyl-L-carnitine (ALC) in dementia, suggesting a role in slowing down cognitive decline. Nevertheless, in 2003 a systematic review concluded there was insufficient evidence to recommend a clinical use, although a meta-analysis in the same year showed a significant advantage for ALC for clinical scales and psychometric tests. Since then, other studies have been published; however, a critical review is still lacking. We provide an update of the studies on ALC in primary and secondary dementia, highlighting the current limitations and translational implications. Overall, the role of ALC in dementia is still under debate. The underlying mechanisms may include restoring of cell membranes and synaptic functioning, enhancing cholinergic activity, promoting mitochondrial energy metabolism, protecting against toxins, and exerting neurotrophic effects. The effects of ALC on the gut-liver-brain axis seem to identify the category of patients in which the new insights contribute most to the mechanisms of action of ALC, likely being the liver metabolism and the improvement of hepatic detoxifying mechanisms the primary targets. In this framework, our research group has dealt with this topic, focusing on the ALC-related cross-talk mechanisms. Further studies with homogeneous sample and longitudinal assessment are needed before a systematic clinical application.

Decrease in Serum Vitamin D Level of Older Patients with Fatigue.

Fatigue is characterized by reduced energy level, decreased muscle strength, and a variable degree of cognitive impairment. Recent evidences seem to link vitamin D deficiency to fatigue. The aim of this study was to assess and compare vitamin D status in a cohort of older subjects with and without fatigue. We recruited a total of 480 subjects, 240 patients with fatigue and 240 controls without fatigue, from the Cannizzaro Hospital of Catania (Italy). Fatigue severity was measured by the fatigue severity scale, whereas mental and physical fatigue were measured through the Wessely and Powell fatigue scale, respectively. We also measured several blood parameters and 25-OH vitamin D. Subjects with fatigue showed lower levels of vitamin D as compared with those without fatigue. Blood levels of parameters related to fatigue were normal in both groups of subjects, however, platelet, hemoglobin, hematocrit (p < 0.05), mean corpuscular volume, C-reactive protein (CRP), iron, vitamin B12, and folic acid (p < 0.001) were significantly higher in the fatigue group with respect to the control group. Moreover, compared to controls, patients showed higher scores in the physical (p < 0.001), mental (p < 0.001), and severity (p < 0.001) fatigue scales. Finally, vitamin D inversely correlated with fatigue severity (r = -0.428, p < 0.01), whereas creatine kinase and CRP levels did not correlate with vitamin D. In conclusion, our data showed a direct link between vitamin D and fatigue in older subjects, suggesting translational implications in the diagnosis and management of these patients.

Homocysteine Serum Levels as Prognostic Marker of Hepatocellular Carcinoma with Portal Vein Thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) is a common complication of endstage hepatocellular carcinoma (HCC). The aim of our study was to evaluate the role of Homocysteine (Hcy) in HCC patient with PVT. Hcy is a sulphur amino-acid involved in two pathways, trans-sulphuration and remethylation, that involve vitamins B6, B12 and folates. METHODS: We recruited 54 patients with HCC and PVT, 60 patients with HCC and without PVT and 60 control subjects. We measured serum levels of Hcy, folate, vitamins B6 and B12. RESULTS: The comparison between HCC patients with PVT versus HCC without PVT was shown that mean values of Hcy were 6.4 nmol/L (p<0.0073) higher, LDL cholesterol were 4.8 mg/dl (p<0.0079) lower, vitamin B6 were 4.6 nmol/L(p=0.0544) lower, vitamins B 12 were 22.1 pg/ml (p=0.0001) lower. CONCLUSION: High serum levels of Hcy are an established thrombotic risk factor in the general population. We found significantly higher levels of Hcy in HCC patients with PVT versus both HCC patients without PVT and controls.

Vitamin D Serum Levels in Patients with Statin-Induced Musculoskeletal Pain.

INTRODUCTION: Statin-associated muscle symptoms are common side effects of statin therapy. These symptoms include myopathy, myalgia, and rhabdomyolysis. Vitamin D has been associated with musculoskeletal health; thus, its deficiency may produce detrimental effects in this tissue. Indeed, one symptom of vitamin D deficiency is myalgia, and the normalization of low vitamin D levels can relieve it. PATIENTS AND METHODS: This cross-sectional study examined 1210 statin-treated patients to assess vitamin D status. These patients were divided into two groups: 287 with statin-associated muscle symptoms (SAMS) and 923 control patients without SAMS. RESULTS: We have found a significant association between deficient and insufficient vitamin D status and statin-associated muscle symptoms (SAMS). Vitamin D deficiency (<30 nmol/L) presents 77% (95% C.I. 71.6% to 81.7%) sensitivity and 63.4% (95% C.I. 60.2% to 66.5%) specificity in diagnosing SAMS. Odds ratio analysis showed that this association is moderate-strong both for deficient and for insufficient status. CONCLUSION: We found a correlation between vitamin D deficiency and SAMS. Therefore, vitamin D levels may be useful for the diagnosis and management of SAMS.

Human Fasciolosis in Iran: A Meta-analysis Study.

BACKGROUND: Fasciolosis, an infectious disorder with a serious public health burden, is caused by two liver flukes belonging to the genus Fasciola. Iran is among the endemic areas for this disease. This study aimed to determine the seroprevalence of human fasciolosis in Iran. METHODS: A systematic search was conducted in Embase, PubMed/MEDLINE, Web of Science (WoS), and Google Scholar, as well as Iranian databases including Scientific Information Database (SID), Magiran and Irandoc from January 2000 to June 2016. In order to determine fasciolosis prevalence, the DerSimonian-Laird random model was used. In order to assess the heterogeneity among studies, I2 and Q tests were used. To investigate the source of heterogeneity, meta-regressions based on the year of publication and sample size were performed. Sensitivity analysis was carried out to ensure the stability of obtained results. RESULTS: Eleven relevant studies were included. According to the data analysis a prevalence rate of 2% [95% CI 1-5] was found. No statistically significant relationship between gender and disease prevalence could be detected. We found an OR of developing fasciolosis of 1.67 [95% CI: 0.42 - 6.60] in people who had consumed vegetables versus those who did not eat vegetables, even though this did not yield statistical significance. CONCLUSION: The findings of the current study can be valuable and help the health-care workers and policy-makers in programming and implementing ad hoc interventions in order to prevent the incidence of disease.

D-dimer plasmatic levels as a marker for diagnosis and prognosis of hepatocellular carcinoma patients with portal vein thrombosis.

PURPOSE: Portal vein thrombosis (PVT) is one of the severe complications of hepatocellular carcinoma (HCC). PVT deteriorates the liver, and its dysfunction increases the risk of bleeding, influencing the prognosis of patients with liver cirrhosis and HCC. The aim of our study was to investigate whether D-dimer testing could be a sensitive marker for the diagnosis and prognosis of HCC patients with PVT. PATIENTS AND METHODS: Between June 2010 and December 2015, 118 HCC patients were admitted to Cannizzaro Hospital, Catania, and 50 controls were recruited from their relatives for health examinations. All enrolled patients were diagnosed and pathologically confirmed as having HCC. D-dimer was measured with an enzyme-linked immunosorbent assay using 2 monoclonal antibodies against nonoverlapping determinants of D-dimer. RESULTS: D-dimer levels in HCC patients with PVT were significantly higher vs HCC patients without PVT, P<0.002, and vs controls, P<0.001. CONCLUSION: Plasma D-dimer is a sensitive marker of fibrin turnover and allows for the recognition of activated coagulation which may be manifested in HCC with PVT.

Differentially Enhancing Effects of Long-term Treatment with Serrazyme, Boswellia and Pine on Seminal Bacterial Detection in Patients with Chronic Bacterial or Inflammatory Prostatitis, Probably Related to Several Degrees of Bacterial Adherence.

BACKGROUND: Prostatitis is a recurrent urinary infection in males and is often difficult to cure. The aim of the study was to examine whether anti-inflammatory effects of enhanced drainage of prostatic secretions, obtained through two months treatment with a proteolytic enzyme mucoactive (PEM) compound (Serrazyme and other constituents), influenced qualitative or quantitative expressions of bacterial growth in seminal cultures. METHOD: 450 patients with prostatitis syndromes were randomized either to PEM therapy (intervention group) or to no treatment group. All patients were followed at the end of a 2-month PEM continuous treatment period (T2) and further two months after withdrawal (T4). RESULTS: After treatment, 15 out of 107 (14.1%) patients with Chronic Bacterial Prostatitis (CBP) showed negative seminal cultures, while in patients with cat NIH-IIIA prostatitis seminal cultures became positive in 33.3% cases with low bacteriospermia. After two months from withdrawal, although among CBP patients the total number of isolates and colony forming units (CFU) counts showed not significant changes compared to matched-values observed at T2, microbial parameters varied significantly among inflammatory prostatitis patients. CONCLUSION: The results of the present study showed that 2 months of treatment with PEM, decreasing bacterial adherence and inflammatory prostatitis, reveals a subgroup of apparent inflammation associated with infection that microbial biofilms likely mask in inflammatory prostatitis patients.

Responsibility of hepatitis C virus in the development of hepatocellular carcinoma: From molecular alterations to possible solutions.

There are several causes of hepatocellular carcinoma (HCC), but certainly the hepatitis C virus (HCV) is one of the most common. The HCV is able to contribute, both directly and indirectly, to the development of HCC. Determining early HCV clearance before an advanced liver disease develops, is absolutely necessary as this prevents the initiation of the cascade of events induced by HCV that may result in the development of HCC. The early treatment of the infection and the clearance of HCV represents today, in the age of the direct antiviral agents (DAAs), an extraordinary opportunity for true prevention of the development of HCV-related HCC.

Topical Curcumin Nanocarriers are Neuroprotective in Eye Disease.

Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5dione) is a polyphenol extracted from turmeric that has long been advocated for the treatment of a variety of conditions including neurodegenerative and inflammatory disorders. Despite this promise, the clinical use of curcumin has been limited by the poor solubility and low bioavailability of this molecule. In this article, we describe a novel nanocarrier formulation comprising Pluronic-F127 stabilised D-α-Tocopherol polyethene glycol 1000 succinate nanoparticles, which were used to successfully solubilize high concentrations (4.3 mg/mL) of curcumin. Characterisation with x-ray diffraction and in vitro release assays localise curcumin to the nanocarrier interior, with each particle measuring <20 nm diameter. Curcumin-loaded nanocarriers (CN) were found to significantly protect against cobalt chloride induced hypoxia and glutamate induced toxicity in vitro, with CN treatment significantly increasing R28 cell viability. Using established glaucoma-related in vivo models of ocular hypertension (OHT) and partial optic nerve transection (pONT), topical application of CN twice-daily for three weeks significantly reduced retinal ganglion cell loss compared to controls. Collectively, these results suggest that our novel topical CN formulation has potential as an effective neuroprotective therapy in glaucoma and other eye diseases with neuronal pathology.

Iatrogenic nerve lesion following laparoscopic surgery. A case report.

BACKGROUND: Peripheral neuropathy after surgical treatment is an under recognized potential untoward event. Pelvic surgery may be associated with nerve lesions by essentially three main mechanisms: transection, entrapment and pressure-stretching; the latter is the modality most frequently linked to patient's positioning on the operating room table. PRESENTATION OF THE CASE: A 25 years old woman, after undergoing a laparoscopic gynaecologic procedure lasted >3 hours, on postoperative day one presented with numbness over her lateral right leg and dorsum of the foot, right foot drop and gait instability due to compression-stretching of the right superficial peroneal nerve. DISCUSSION: Patient's diagnostic work up, treatment and outcome are reported and measures on how to prevent the occurrence of such type of lesion are outlined together with the importance of an early postoperative diagnosis in order to avoid permanent nerve damage. CONCLUSION: Such lesions are sometimes so unexpected that delayed diagnosis leads to damages which are difficult or impossible to repair. Primary prevention plays a key role and it is realized by adhering to specific protocols. In the occurrence of the lesion a prompt diagnosis is highly recommendable and a comprehensive therapeutic plan is necessary to correctly address the specific pathology.

Progressive Supranuclear Palsy: Neuropsychopathological, Therapeutical and Bioethical Aspects.

The progressive supranuclear palsy is a progressive neurodegenerative disease characterized by Parkinsonism, oculomotor abnormalities, early postural instability and cognitive impairment. Neurodegeneration in PSP is associated with tau protein, but the mechanisms by which tau abnormalities lead to cell dysfunction and death are not well understood. Neuro-behavioural problems related to the fear and loss of autonomy can determinate many bioethical implications. Careful planning involving patients' families, academic and industry researchers were necessary to ensure improvement in quality of life.