Telesurgical mentoring

Background: Minimally invasive surgical techniques yield significant individual, economic, and social benefits when performed by experienced surgeons. Unfortunately, many of these techniques, such as laparoscopy, are associated with steep learning curves, and the incidence of complications has clearly been shown to be inversely related to experience. The initial high complication rate and the dearth of experienced endoscopic surgeons have raised concerns over training, granting of hospital privileges, and most importantly patient safety. The goal of this study was to employ current telecommunications technology in a system for the mentoring of relatively inexperienced surgeons. Therefore, we created a telesurgical system that would allow an endoscopic specialist at a central site to offer guidance and assistance to a surgeon during a laparoscopic procedure. Methods: We developed a system that connected a central site and an operative site, a distance of approximately 3.5 miles, via a single T1 (1.54 Mbs) point-to-point communications link. The system provided real-time video display from either the laparoscope or an externally mounted camera located in the operating room, full duplex audio, telestration over live video, control of a robotic arm that manipulated the laparoscope, and access to electrocautery for tissue cutting or hemostasis. Results: Seven patients underwent laparoscopic procedures using the telesurgical consultation system over the communications link. In all cases, the primary surgeon had limited experience with the laparoscopic approach but still had the basic skills required to obtain intraperitoneal access. All seven cases were completed successfully without complications. Conclusion: These initial studies have demonstrated the feasibility, effectiveness, and safety of telementoring. Telesurgical applications have the potential to greatly improve surgical education, credentialing, and patient care by offering patients and their surgeons global access to surgical specialists.     

Botulinum toxin B ultrasound-guided injections for sialorrhea in amyotrophic lateral sclerosis and Parkinson's disease

Sialorrhea is frequent and invalidating in patients with amyotrophic lateral sclerosis (ALS) or Parkinson's disease (PD). Botulinum toxin (BTX) emerged as an alternative to traditional treatments. We evaluated efficacy and tolerability of ultrasound-guided BTX-B injections in parotids and submandibular glands in 18 patients with ALS or PD. At 1 week, both objective (cotton rolls weight) and subjective evaluations (dedicated clinical scales) documented sialorrhea reduction (p<0.01). ALS patients reported shorter benefit duration (p<0.001) and higher prevalence of viscous saliva (seven vs one patients), possibly due to different pattern of autonomic involvement. BTX-B seems efficacious in reducing sialorrhea in ALS and PD but the risk-benefit ratio might differ between these two conditions. This might have implications for clinical practice.     

Adrenocortical oncocytic tumors: report of 10 cases and review of the literature

Ten additional adrenocortical oncocytic tumors are presented: 2 benign oncocytomas, 4 borderline oncocytomas of uncertain malignant potential, and 4 oncocytic carcinomas. Histologically all tumors were entirely or predominantly composed of oncocytes. Immunohistochemically all tumors were immunoreactive for mitochondrial antigen mES-13. Electron microscopy was performed in 8 cases and was confirmatory of the oncocytic cell change. The morphologic parameters of the Weiss system, considered to be predictive of the biologic behavior of conventional (nononcocytic) adrenocortical tumors, are reviewed in the context of their possible application to the oncocytic tumor variant. Proposed major criteria (high mitotic rate, atypical mitoses, venous invasion) and minor criteria (large size and huge weight, necrosis, capsular invasion, sinusoidal invasion) in distinguishing malignant tumors are discussed, and definitional criteria (predominantly cells with eosinophilic and granular cytoplasm, high nuclear grade, diffuse architectural pattern) in common with all types of oncocytic tumors are outlined. The authors' proposed working rules for diagnostic categorization of oncocytic adrenocortical tumors are defined, with the presence of 1 major criterion indicating malignancy, 1 to 4 minor criteria indicating uncertain malignant potential (borderline), and the absence of all major and minor criteria indicative of benignancy. Using these criteria, the diagnosis of malignancy was straightforward in 3 of the 4 cases designated as oncocytic carcinoma (presence of at least 2 major criteria and all the minor criteria), while in 1 case the original diagnosis of benign oncocytoma was reversed to malignant following critical review of the original pathologic material after local tumor recurrence. Tumor recurrence occurred in 2 carcinomas at 8 and 20 months, respectively, and was followed in 1 case by the patient's death. The third patient expired at 6 months from unrelated causes, and the fourth patient is free of disease at the relatively short follow-up interval of 6 months. Regarding the 4 patients with borderline tumors, all are alive with no evidence of disease, with follow-up ranging from 10 to 61 months (mean 38.7 months). The 2 benign tumors have a follow-up of 25 and 30 months, respectively. Diagnostic difficulties are delineated and a complete review of the literature on this topic has also been performed.     

Neuronal inclusions of α‐synuclein contribute to the pathogenesis of Krabbe disease

Demyelination is a major contributor to the general decay of neural functions in children with Krabbe disease. However, recent reports have indicated a significant involvement of neurons and axons in the neuropathology of the disease. In this study, we have investigated the nature of cellular inclusions in the Krabbe brain. Brain samples from the twitcher mouse model for Krabbe disease and from patients affected with the infantile and late‐onset forms of the disease were examined for the presence of neuronal inclusions. Our experiments demonstrated the presence of cytoplasmic aggregates of thioflavin‐S‐reactive material in both human and murine mutant brains. Most of these inclusions were associated with neurons. A few inclusions were detected to be associated with microglia and none were associated with astrocytes or oligodendrocytes. Thioflavin‐S‐reactive inclusions increased in abundance, paralleling the development of neurological symptoms, and distributed throughout the twitcher brain in areas of major involvement in cognition and motor functions. Electron microscopy confirmed the presence of aggregates of stereotypic β‐sheet folded proteinaceous material. Immunochemical analyses identified the presence of aggregated forms of α‐synuclein and ubiquitin, proteins involved in the formation of Lewy bodies in Parkinson's disease and other neurodegenerative conditions. In vitro assays demonstrated that psychosine, the neurotoxic sphingolipid accumulated in Krabbe disease, accelerated the fibrillization of α‐synuclein. This study demonstrates the occurrence of neuronal deposits of fibrillized proteins including α‐synuclein, identifying Krabbe disease as a new α‐synucleinopathy. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd     

Investigation of 3111T/C polymorphism of the CLOCK gene in obese individuals with or without binge eating disorder: association with higher body mass index

Loss of circadian patterning of metabolism-related functions seems to play a role in the pathogenesis of obesity; therefore, it is reasonable to hypothesize that the functional 3111T/C single nucleotide polymorphism (SNP) of the (Circadian locomotor output cycles kaput) CLOCK gene may have a part in the genetic susceptibility to obesity. The aim of this study was to assess the frequencies of 3111T/C CLOCK gene SNP in overweight/obese subjects with or without binge eating disorder (BED) as compared to normal weight healthy controls. A total of 284 Caucasian subjects, including 92 normal weight healthy subjects and 192 overweight/obese patients (107 with BED) participated into the study. Genotype and allele frequencies did not significantly differ between normal weight controls and overweight/obese patients with and/or without BED. However, overweight/obese patients carrying the CC genotype had significantly higher values of body mass index (BMI) as compared to those carrying the CT and/or TT genotypes. Moreover, obese class III individuals had a significantly higher frequency of both the CC genotype and the C allele as compared to individuals with BMI<40 kg/m(2). Present findings show for the first time that the 3111T/C SNP of the CLOCK gene is not associated to human obesity and/or BED, but it seems to predispose obese individuals to a higher BMI.     

An SPR based immunoassay for the sensitive detection of the soluble epithelial marker E-cadherin

Protein biomarkers are important diagnostic tools for cancer and several other diseases. To be validated in a clinical context, a biomarker should satisfy some requirements including the ability to provide reliable information on a pathological state by measuring its expression levels. In parallel, the development of an approach capable of detecting biomarkers with high sensitivity and specificity would be ideally suited for clinical applications. Here, we performed an immune-based label free assay using Surface Plasmon Resonance (SPR)-based detection of the soluble form of E-cadherin, a cell–cell contact protein that is involved in the maintaining of tissue integrity. With this approach, we obtained a specific and quantitative detection of E-cadherin from a few hundred microliters of serum of breast cancer patients by obtaining a 10-fold enhancement in the detection limit over a traditional colorimetric ELISA.     

Dietary Polyphenols and Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD), which is emerging as a major public health issue worldwide, is characterized by a wide spectrum of liver disorders, ranging from simple fat accumulation in hepatocytes, also known as steatosis, to non-alcoholic steatohepatitis (NASH) and cirrhosis. At present, the pharmacological treatment of NAFLD is still debated and dietary strategies for the prevention and the treatment of this condition are strongly considered. Polyphenols are a group of plant-derived compounds whose anti-inflammatory and antioxidant properties are associated with a low prevalence of metabolic diseases, including obesity, hypertension, and insulin resistance. Since inflammation and oxidative stress are the main risk factors involved in the pathogenesis of NAFLD, recent studies suggest that the consumption of polyphenol-rich diets is involved in the prevention and treatment of NAFLD. However, few clinical trials are available on human subjects with NAFLD. Here, we reviewed the emerging existing evidence on the potential use of polyphenols to treat NAFLD. After introducing the physiopathology of NAFLD, we focused on the most investigated phenolic compounds in the setting of NAFLD and described their potential benefits, starting from basic science studies to animal models and human trials.