Risk factors for surgical complications after central pancreatectomy

Background/Aims: Central pancreatectomy is a pancreas- sparing alternative to standard pancreatic resections in selected cases. Although associated with high morbidity, the risk factors for surgical complications of this procedure are not yet defined. Methodology: The clinicopathological and perioperative data of 24 patients who underwent central pancreatectomies (2002-2010) were correlated with surgical complications. Results: The overall morbidity rate was 54% (pancreatic fistula, 40%). In a univariate analysis, age over 40 years, body mass index ≥30kg/m2, smoking and American Society of Anesthesiologists III scores were significantly correlated with increased morbidity. In a multivariate analysis, a significant correlation with the development of complications was found for body mass index ≥30kg/m2 and age over 40 years. Conclusions: Certain patient-related factors (older age, obesity and smoking) appear to have a negative impact on early postoperative outcome after central pancreatectomy. For patients with these factors, an alternative distal pancreatectomy should be considered. Central pancreatectomy should be tailored not only to the pathology but also to the patient profile.     

N-Linked Glycosylation on Anthrax Toxin Receptor 1 Is Essential for Seneca Valley Virus Infection

Seneca Valley virus (SVV) is a picornavirus with potency in selectively infecting and lysing cancerous cells. The cellular receptor for SVV mediating the selective tropism for tumors is anthrax toxin receptor 1 (ANTXR1), a type I transmembrane protein expressed in tumors. Similar to other mammalian receptors, ANTXR1 has been shown to harbor N-linked glycosylation sites in its extracellular vWA domain. However, the exact role of ANTXR1 glycosylation on SVV attachment and cellular entry was unknown. Here we show that N-linked glycosylation in the ANTXR1 vWA domain is necessary for SVV attachment and entry. In our study, tandem mass spectrometry analysis of recombinant ANTXR1-Fc revealed the presence of complex glycans at N166, N184 in the vWA domain, and N81 in the Fc domain. Symmetry-expanded cryo-EM reconstruction of SVV-ANTXR1-Fc further validated the presence of N166 and N184 in the vWA domain. Cell blocking, co-immunoprecipitation, and plaque formation assays confirmed that deglycosylation of ANTXR1 prevents SVV attachment and subsequent entry. Overall, our results identified N-glycosylation in ANTXR1 as a necessary post-translational modification for establishing stable interactions with SVV. We anticipate our findings will aid in selecting patients for future cancer therapeutics, where screening for both ANTXR1 and its glycosylation could lead to an improved outcome from SVV therapy.     

Cryo-EM Structure of a Possum Enterovirus

Enteroviruses (EVs) represent a substantial concern to global health. Here, we present the cryo-EM structure of a non-human enterovirus, EV-F4, isolated from the Australian brushtail possum to assess the structural diversity of these picornaviruses. The capsid structure, determined to ~3 Å resolution by single particle analysis, exhibits a largely smooth surface, similar to EV-F3 (formerly BEV-2). Although the cellular receptor is not known, the absence of charged residues on the outer surface of the canyon suggest a different receptor type than for EV-F3. Density for the pocket factor is clear, with the entrance to the pocket being smaller than for other enteroviruses.     

Klatskin-mimicking lesions--a case series and literature review

Obstruction of the hepatic hilum in patients without prior surgery is generally due to hilar adenocarcinoma (Klatskin tumor). However, not all the hilar strictures are malignant. Although uncommon, benign strictures of the proximal bile duct should be taken into consideration in differential diagnosis of Klatskin tumors, since the incidence could reach up to 25% of patients with presumed Klatskin tumor diagnosis. This group of benign proximal bile duct strictures (Klatskin-mimicking lesions) is usually represented by segmental fibrosis and non-specific chronic inflammation. The clinical and imaging features can not differentiate between benign and malignant strictures. Herein, we present a case series of three patients with benign proximal bile duct strictures (representing 4.1% of 73 patients resected with presumptive preoperative diagnosis of Klatskin tumor) and literature review. There are presented the clinical and biochemical features, imaging preoperative workup, surgical treatment and histological analysis of the specimen, along with postoperative outcome. For benign strictures of the hilum limited resections are curative. However, despite new diagnosis tools developed in the last years, patients with hilar obstructions still require unnecessary extensive resections due to impossibility of excluding the malignancy. In all cases of proximal bile duct obstruction presumed malignant, they should be managed accordingly, even with the risk of over-treatment for some benign lesions.     

Vitamin D modulation of innate immune responses to respiratory viral infections

Vitamin D, in addition to its classical functions in bone homeostasis, has a modulatory and regulatory role in multiple processes, including host defense, inflammation, immunity, and epithelial repair. Patients with respiratory disease are frequently deficient in vitamin D, implying that supplementation might provide significant benefit to these patients. Respiratory viral infections are common and are the main trigger of acute exacerbations and hospitalization in children and adults with asthma and other airways diseases. Respiratory monocytes/macrophages and epithelial cells constitutively express the vitamin D receptor. Vitamin D, acting through this receptor, may be important in protection against respiratory infections. Whether the in vitro findings can be translated into a substantial in vivo benefit still remains uncertain. Here we review the in vitro data on the role of vitamin D in antiviral innate immunity, the data concerning the deficient levels of vitamin D in lung diseases, and the in vivo role of supplementation as protection against respiratory viral infections in healthy individuals and in patients with chronic respiratory diseases. Finally, we suggest ways of improving the effectiveness of vitamin D as an adjuvant in the prevention and treatment of acute respiratory infections.     

Severe adverse events during antiviral therapy in hepatitis C virus cirrhotic patients: A systematic review

AIM: To identify severe adverse events (SAEs) leading to treatment discontinuation that occur during antiviral therapy in hepatitis C virus (HCV)-infected cirrhotic patients.METHODS: We identified all the articles published prior to December 2011 in the PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases that presented these data in cirrhotic patients. These studies evaluated the rate of SAEs leading to discontinuation of standard care treatment: Pegylated interferon (PegIFN) alpha 2a (135-180 μg/wk) or PegIFN alpha 2b (1 or 1.5 μg/kg per week) and ribavirin (800-1200 mg/d). Patients with genotype 1 + 4 underwent treatment for 48 wk, whereas those with genotypes 2 + 3 were treated for 24 wk.RESULTS: We included 17 papers in this review, comprising of 1133 patients. Treatment was discontinued due to SAEs in 14.5% of the patients. The most common SAEs were: severe thrombocytopenia and/or neutropenia (23.2%), psychiatric disorders (15.5%), decompensation of liver cirrhosis (12.1%) and severe anemia (11.2%). The proportion of patients who needed to discontinue their therapy due to SAEs was significantly higher in patients with Child-Pugh class B and C vs those with Child-Pugh class A: 22% vs 11.4% (P = 0.003). A similar discontinuation rate was found in cirrhotic patients treated with PegIFN alpha 2a and those treated with PegIFN alpha 2b, in combination with ribavirin: 14.2% vs 13.7% (P = 0.96). The overall sustained virological response rate in cirrhotic patients was 37% (95%CI: 33.5-43.1) but was significantly lower in patients with genotype 1 + 4 than in those with genotype 2 + 3: 20.5% (95%CI: 17.9-24.8) vs 56.5% (95%CI: 51.5-63.2), (P < 0.0001).CONCLUSION: Fourteen point five percent of HCV cirrhotic patients treated with PegIFN and ribavirin needed early discontinuation of therapy due to SAEs, the most common cause being hematological disorders.     

Genome,Proteome and Structure of a T7-Like Bacteriophage of the Kiwifruit Canker Phytopathogen Pseudomonas syringae pv. actinidiae

Pseudomonas syringae pv. actinidiae is an economically significant pathogen responsible for severe bacterial canker of kiwifruit (Actinidia sp.). Bacteriophages infecting this phytopathogen have potential as biocontrol agents as part of an integrated approach to the management of bacterial canker, and for use as molecular tools to study this bacterium. A variety of bacteriophages were previously isolated that infect P. syringae pv. actinidiae, and their basic properties were characterized to provide a framework for formulation of these phages as biocontrol agents. Here, we have examined in more detail φPsa17, a phage with the capacity to infect a broad range of P. syringae pv. actinidiae strains and the only member of the Podoviridae in this collection. Particle morphology was visualized using cryo-electron microscopy, the genome was sequenced, and its structural proteins were analysed using shotgun proteomics. These studies demonstrated that φPsa17 has a 40,525 bp genome, is a member of the T7likevirus genus and is closely related to the pseudomonad phages φPSA2 and gh-1. Eleven structural proteins (one scaffolding) were detected by proteomics and φPsa17 has a capsid of approximately 60 nm in diameter. No genes indicative of a lysogenic lifecycle were identified, suggesting the phage is obligately lytic. These features indicate that φPsa17 may be suitable for formulation as a biocontrol agent of P. syringae pv. actinidiae.     

Male gender and increased body mass index independently predicts clinically relevant morbidity after spleen-preserving distal pancreatectomy

AIM To identify risk factors for clinically relevant complications after spleen-preserving distal pancreatectomy(SPDP). No previous studies explored potential predictors of morbidity after SPDP.METHODS The data of 41 patients who underwent a SPDP in a single surgical center between 2000 and 2015 were retrospectively reviewed from a prospectively maintained electronic database established in our Department of Surgery. The database included demographic, clinical, bioumoral, pathological, intraoperative and postoperative parameters. Uni-and multivariate ana-lyses were performed to assess potential predictors of clinically relevant morbidity. Postoperative morbidity was defined as in-hospital complications and mortality was assessed at 90 d. Clinically relevant morbidity was defined as complication ≥ grade 2 Dindo.RESULTS Overall morbidity rate was 34.1%(14 patients): grade Ⅰ(6 patients, 14.6%), grade Ⅱ(2 patients, 4.8%), grade Ⅲa(1 patient, 2.4%), and grade Ⅲb(5 patients, 12.2%). A number of 5 patients(12.2%) required re-laparotomy for postoperative complications. There was no postoperative mortality. Thus, at least one clinically relevant complication occurred in 8 patients(19.5%). Univariate analysis identified male gender(P = 0.034), increased body mass index(P = 0.002) and neuroendocrine pathology(P = 0.013) as statistically significant risk factors. Multivariate analysis identified male gender [odds ratio(OR): 1.29, 95%CI: 1.07-1.55, P = 0.005] and increased body mass index(OR: 23.18, 95%CI: 1.72-310.96, P = 0.018) as the only independent risk factors of clinically relevant morbidity after SPDP.CONCLUSION Male gender and increased body mass index are independently associated with increased risk of clinically relevant morbidity after SPDP. These findings may assist a surgeon in clinical decision-making to better select patients suitable for SPDP.