Pathological Margin Clearance and Survival After Pancreaticoduodenectomy in a US and European Pancreatic Center

Background: The optimal definition of a margin-negative resection and its exact prognostic significance on survival in resected pancreatic adenocarcinoma remains unknown. This study was designed to assess the relationship between pathological margin clearance, margin type, and survival. Methods: Patients who underwent pancreaticoduodenectomy with curative intent at two academic institutions, in Amsterdam, the Netherlands, and Boston, Massachusetts, between 2000 and 2014 were retrospectively evaluated. Overall survival, recurrence rates, and progression-free survival (PFS) were assessed by Kaplan–Meier estimates and multivariate Cox proportional hazards analysis, according to pathological margin clearance and type of margin involved. Results: Of 531 patients identified, the median PFS was 12.9, 15.4, and 24.1 months, and the median overall survival was 17.4, 22.9, and 27.7 months for margin clearances of 0, < 1, and ≥1 mm, respectively (all log-rank p < 0.001). On multivariate analysis, patients with a margin clearance of ≥1 mm demonstrated a survival advantage relative to those with 0 mm clearance [hazard ratio (HR) 0.71, p < 0.01], whereas survival was comparable for patients with a margin clearance of < 1 mm versus 0 mm (HR: 0.93, p = 0.60). Patients with involvement (0 or < 1 mm margin clearance) of the SMV/PV margin demonstrated prolonged median overall survival (25.7 months) relative to those with SMA involvement (17.5 months). Conclusions: In patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, a margin clearance of ≥1 mm correlates with improved survival relative to < 1 mm clearance and may be a more accurate predictor of a complete margin-negative resection in pancreatic cancer. The type of margin involved also appears to impact survival. Electronic supplementary material The online version of this article (10.1245/s10434-018-6467-9) contains supplementary material, which is available to authorized users

Therapeutic targeting of Toll-like receptors in cutaneous disorders

INTRODUCTION: The role of skin, as a part of the immune system has long been elucidated. Toll-like receptors (TLRs), a group of pattern recognition receptors, are involved in the recognition of invading pathogens, initiation of immune responses and regulation of both innate and adaptive immune systems. There is a growing body of evidence supporting the role of TLRs in the pathophysiology of several skin conditions, which mandates the development and study of therapeutic strategies that target TLRs. AREAS COVERED: With regards to the role of TLRs in pathogenesis of diverse cutaneous conditions, recent advances, as well as the future prospects of therapeutic implications of TLRs in cutaneous disorders is reviewed in this article. EXPERT OPINION: Although non-specific therapeutic strategies seem to reduce the symptoms in majority of patients, a considerable proportion remain untreated or have to deal with inevitable adverse effects of such therapies. Since TLRs regulate many patholophysiological processes, they could be good candidates for more specific therapeutic approaches. TLR targeting as the first recipient of invading pathogens is a growing concept in this field

Development and validation of osteoporosis prescreening model for Iranian postmenopausal women

BACKGROUND: Studies have indicated that the commonly used osteoporosis prescreening tools are not appropriate for use in every nation. This study was designed to develop and validate a prescreening model for bone mineral densitometry among Iranian postmenopausal women. METHODS: From 13613 individuals who were referred for bone mineral densitometry in Shariati hospital in Tehran, 8644 postmenopausal women were considered for the study after excluding men and premenopausal women. Questionnaires regarding the risk factors for osteoporosis were filled for each individual. Bone mineral density at the lumbar vertebrae (L2-L4), femoral neck and total femur was measured by dual X-ray absorptiometry. Using holdout validation, the study sample was divided into two parts; training set (5705) and test set (2939). Logistic regression analysis was performed on the training set. A scoring model was developed and tested in the test set. RESULTS: Based on the training set, a seven-variable model named OPMIP (Osteoporosis Prescreening Model for Iranian Postmenopausal women) was developed with C statistics (area under curve) of 0.72. Using a cut-off of -2.5 for the model, the sensitivity, specificity, positive predictive value and negative predictive value were 72%, 59.5%, 64% and 69% respectively. The model performance was tested in the test set. OPMIP correctly classified 67.10% of cases with a sensitivity and specificity of 73.2% and 61%. CONCLUSIONS: In order to appropriately refer patients for a bone mineral densitometry, OPMIP can be used as a prescreening tool in Iranian Postmenopausal women

Nervous system involvement in clinical peripheral inflammation: A description of three pediatric cases

Latest research data have emphasized the interaction between the nervous and the immune systems. In this regard, it has been demonstrated that the disruption of the blood–brain barrier (BBB) secondary to peripheral inflammation may play a key role in this relationship. This assumption is linked to recent findings according to which units that constitute the BBB are not only simply neurologic but have also been reconsidered as “neurovascular” elements, through which immune system molecules are vehiculated within the central nervous system (CNS). Herein, we report two cases of food allergy (FA) and one case of infective gastroenteritis, associated with a spectrum of neurologic disorders involving both the CNS and the peripheral nervous system (PNS), postulating some etiopathogenic hypotheses to explain the link between peripheral inflammation and diseases of the nervous system (NS). Three pediatric cases of secondary NS involvement after gastrointestinal (GI) inflammation of different nature have been reported. The first case highlights the link between FA and CNS; the second one is based on a description of a link between GI infection and CNS involvement while the third one describes the relationship between FA and PNS. The importance of these reports relies on the clinical demonstration of a link between the immune system and the NS. The relationship between immune system and NS seems to have pleiotropic aspects, involving different areas of the NS, such as CNS and PNS, which also seem to be in some way interconnected

Clinical performance of seven prescreening tools for osteoporosis in Iranian postmenopausal women

This study was designed to evaluate seven prescreening osteoporosis models in postmenopausal Iranian women. This study was performed on 8644 postmenopausal women who have been referred for bone mineral densitometry (BMD) in BMD center of Shariati hospital in Tehran between 2001 and 2011. Diagnostic properties of seven prescreening instruments were evaluated. With regard to area under curve (AUC), these models have low accuracy (AUC a parts per thousand currency sign 0.65). Considering only femoral neck or total femur area, these models had low accuracy but were more sensitive. Except for three models with sensitivities of a parts per thousand currency sign65 % in both osteoporosis and fracture threshold, other models were around 70 % sensitive. However, these models were not considered clinically useful regarding their positive predictive values (PPV) especially in BMDs a parts per thousand currency sign02.5. With regard to different measures of diagnostic property, none of these models were good screening tools for osteoporosis or fracture threshold. Although some of them are sensitive, considering other measures such as PPV indicates that they are not completely useful for clinical use. Attempts should be made for developing newer prescreening methods and calibration of the existing models with regard to the studied population

Natalizumab in multiple sclerosis: Discontinuation, progressive multifocal leukoencephalopathy and possible use in children

In the early 1990s, attention was drawn to the migration of immune cells into the central nervous system via the blood-brain barrier. The literature showed that lymphocytes binding to the endothelium were successfully inhibited by an antibody against 41 integrin. These biological findings resulted in the development of a humanized antibody to 4 integrin - natalizumab (NTZ) - to treat multiple sclerosis (MS). Here, we provide a systematic review and meta-analysis on the efficacy and safety of natalizumab, trying to answer the question whether its use may be recommended both in adult and in pediatric age groups as standard MS treatment. Our results highlight the improvement of clinical and radiological findings in treated patients (p<0.005), confirming NTZ efficacy. Nevertheless, if NTZ is shown to be efficient, further studies should be performed to evaluate its safety and to target the MS profile that could benefit from this treatment

Biological Drugs in Guillain-Barré Syndrome: An Update

Background: Guillain-Barré Syndrome (GBS) is currently considered the most common global cause of acute flaccid paralysis. Currently, standard therapy for Guillain-Barré Syndrome includes intravenous immunoglobulin or plasma exchange. Despite medical advances regarding these treatments, many treated patients do not reach full recovery. Therefore several biological agents have attracted the attentions from researchers during the last decades, and various studies have investigated their role in Guillain-Barré Syndrome. Objective: The present study aims to address emerging biological approaches to GBS while considering their efficiency and safety in treating the disease. Materials and Methods: An extensive electronic literature search was conducted by two researchers from April 2016 to July 2016. Original articles, clinical trials, systematic reviews (with or without meta-analysis) and case reports were selected. Titles and abstracts of papers were screened by reviewers to determine whether they met the eligibility criteria, and full texts of the selected articles were retrieved. Results: Herein authors focused on the literature data concerning emerging biological therapeutic agents, namely anti-C5 monoclonal antibody (Eculizumab), anti-C1q monoclonal antibody, anti-T cell monoclonal antibody, anti-CD2 monoclonal antibody, anti L-selectin monoclonal antibody, anti-CD20 monoclonal antibody (Rituximab), anti-CD52 monoclonal antibody (Alemtuzumab) and cytokine targets. By far, none of these agents have been approved for the treatment of GBS by FDA. Conclusion: Literature findings represented in current review herald promising results for using these biological targets. Current review represents a summary of what is already in regards and what progress is required to improve the immunotherapeutic approach of treating GBS via future studies

Epilepsy and innate immune system: A possible immunogenic predisposition and related therapeutic implications

Recent experimental studies and pathological analyses of patient brain tissue samples with refractory epilepsy suggest that inflammatory processes and neuroinflammation plays a key-role in the etiopathology of epilepsy and convulsive disorders. These inflammatory processes lead to the secretion of pro-inflammatory cytokines responsible for blood-brain- barrier disruption and involvement of resident immune cells in the inflammation pathway, occurring within the Central Nervous System (CNS). These elements are produced through activation of Toll-Like Receptors (TLRs) by exogenous and endogenous ligands thereby increasing expression of cytokines and co-stimulatory molecules through the activation of TLRs 2, 3, 4, and 9 as reported in murine studies. It has been demonstrated that IL-1b intracellular signaling and cascade is able to alter the neuronal excitability without cell loss. The activation of the IL-1b/ IL-1b R axis is strictly linked to the secretion of the intracellular protein MyD88, which interacts with other cell surface receptors, such as TLR4 during pathogenic recognition. Furthermore, TLR-signaling pathways are able to recognize molecules released from damaged tissues, such as damage-associated molecular patterns/proteins (DAMPs). Among these molecules, High- mobility group box-1 (HMGB1) is a component of chromatin that is passively released from necrotic cells and actively released by cells that are subject to profound stress. Moreover, recent studies have described models of epilepsy induced by the administration of bicuculline and kainic acid that highlight the nature of HMGB1-TLR4 interactions, their intracellular signaling pathway as well as their role in ictiogenesis and epileptic recurrence.The aim of our review is to focus on different branches of innate immunity and their role in epilepsy, emphasizing the role of immune related molecules in epileptogenesis and highlighting the research implications for novel therapeutic strategies

Therapeutic approaches to pediatric pseudotumor cerebri: New insights from literature data

The pseudotumor cerebri syndrome (PTCS), also known as idiopathic intracranial hypertension (IIH), is characterized by signs and symptoms of increased intracranial pressure such as headache and cranial nerve palsies, in the absence of any space-occupying mass. This condition commonly affects overweight women of childbearing age, even if it is also frequent in men and children. Children with PTCS may present with atypical signs and symptoms, with a different prognosis compared to adults. However, the treatment is the same for both children and adults, even if there are no strict treatment guidelines in regards. All treatment strategies in children are based on retrospective studies and none has been evaluated in prospective or randomized controlled trial studies. This review focuses on literature data on PTCS treatment in children