Safe implementation of a minimally invasive hepatopancreatobiliary program, a narrative review and institutional experience.

Laparoscopic and robotic-assisted approaches to hepatopancreatobiliary (HPB) operations have expanded worldwide. As surgeons and medical centers contemplate initiating and expanding minimally invasive surgical (MIS) programs for complex HPB surgical operations, there are many factors to consider. This review highlights the key components of developing an MIS HPB program and shares our recent institutional experience with the adoption and expansion of an MIS approach to pancreaticoduodenectomy.

Host Associations of Culicoides Biting Midges in Northeastern Kansas, USA.

Culicoides biting midges (Diptera: Ceratopogonidae) are hematophagous flies that transmit several viruses of veterinary concern to livestock. Understanding blood feeding behaviors is integral towards identification of putative vector species and preventing the transmission of these pathogens. PCR-based blood meal analysis was conducted on 440 blood-engorged Culicoides midges collected in northeastern Kansas, with 316 (71.8%) returning non-human vertebrate identifications at the ≥95% identity match level. Broadly, Culicoides sonorensis, Culicoides stellifer, and Culicoides variipennis were found to feed heavily on mammalian hosts, while Culicoides crepuscularis and Culicoides haematopotus fed on avian hosts. The blood meals in all specimens were graded prior to DNA extraction to determine whether blood meal size or digestion status significantly impacted the likelihood of a quality host match. Size had a significant impact on the likelihood of a quality match at grades 3-5, whereas digestion only significantly impacted outcomes at the most extreme grade. These vector-host dynamics have not previously been studied in Culicoides collected in Kansas, which represents a unique tallgrass prairie biome within the United States that is heavily interspersed with livestock operations. Based on these data, the highly abundant species C. crepuscularis and C. haematopotus are unlikely to be major vectors of mammalian viruses.

Surgical Management of Retroperitoneal Sarcoma.

Surgery is the cornerstone of treatment for retroperitoneal sarcoma (RPS). Surgery should be performed by a surgical oncologist with sub-specialization in this disease and in the context of a multidisciplinary team of sarcoma specialists. For primary RPS, the goal of surgery is to achieve the complete en bloc resection of the tumor along with involved organs and structures to maximize the clearance of the disease. The extent of resection also needs to consider the risk of complications. Unfortunately, the overarching challenge in primary RPS treatment is that even with optimal surgery, tumor recurrence occurs frequently. The pattern of recurrence after surgery (e.g., local versus distant) is strongly associated with the specific histologic type of RPS. Radiation and systemic therapy may improve outcomes in RPS and there is emerging data studying the benefit of non-surgical treatments in primary disease. Topics in need of further investigation include criteria for unresectability and management of locally recurrent disease. Moving forward, global collaboration among RPS specialists will be key for continuing to advance our understanding of this disease and find more effective treatments.

Mechanism of an intramembrane chaperone for multipass membrane proteins.

Multipass membrane proteins play numerous roles in biology and include receptors, transporters, ion channels and enzymes1,2. How multipass proteins are co-translationally inserted and folded at the endoplasmic reticulum is not well understood2. The prevailing model posits that each transmembrane domain (TMD) of a multipass protein successively passes into the lipid bilayer through a front-side lateral gate of the Sec61 protein translocation channel3-9. The PAT complex, an intramembrane chaperone comprising Asterix and CCDC47, engages early TMDs of multipass proteins to promote their biogenesis by an unknown mechanism10. Here, biochemical and structural analysis of intermediates during multipass protein biogenesis showed that the nascent chain is not engaged with Sec61, which is occluded and latched closed by CCDC47. Instead, Asterix binds to and redirects the substrate to a location behind Sec61, where the PAT complex contributes to a multipass translocon surrounding a semi-enclosed, lipid-filled cavity11. Detection of multiple TMDs in this cavity after their emergence from the ribosome suggests that multipass proteins insert and fold behind Sec61. Accordingly, biogenesis of several multipass proteins was unimpeded by inhibitors of the Sec61 lateral gate. These findings elucidate the mechanism of an intramembrane chaperone and suggest a new framework for multipass membrane protein biogenesis at the endoplasmic reticulum.

A unified evolutionary origin for the ubiquitous protein transporters SecY and YidC.

BACKGROUND: Protein transporters translocate hydrophilic segments of polypeptide across hydrophobic cell membranes. Two protein transporters are ubiquitous and date back to the last universal common ancestor: SecY and YidC. SecY consists of two pseudosymmetric halves, which together form a membrane-spanning protein-conducting channel. YidC is an asymmetric molecule with a protein-conducting hydrophilic groove that partially spans the membrane. Although both transporters mediate insertion of membrane proteins with short translocated domains, only SecY transports secretory proteins and membrane proteins with long translocated domains. The evolutionary origins of these ancient and essential transporters are not known. RESULTS: The features conserved by the two halves of SecY indicate that their common ancestor was an antiparallel homodimeric channel. Structural searches with SecY's halves detect exceptional similarity with YidC homologs. The SecY halves and YidC share a fold comprising a three-helix bundle interrupted by a helical hairpin. In YidC, this hairpin is cytoplasmic and facilitates substrate delivery, whereas in SecY, it is transmembrane and forms the substrate-binding lateral gate helices. In both transporters, the three-helix bundle forms a protein-conducting hydrophilic groove delimited by a conserved hydrophobic residue. Based on these similarities, we propose that SecY originated as a YidC homolog which formed a channel by juxtaposing two hydrophilic grooves in an antiparallel homodimer. We find that archaeal YidC and its eukaryotic descendants use this same dimerisation interface to heterodimerise with a conserved partner. YidC's sufficiency for the function of simple cells is suggested by the results of reductive evolution in mitochondria and plastids, which tend to retain SecY only if they require translocation of large hydrophilic domains. CONCLUSIONS: SecY and YidC share previously unrecognised similarities in sequence, structure, mechanism, and function. Our delineation of a detailed correspondence between these two essential and ancient transporters enables a deeper mechanistic understanding of how each functions. Furthermore, key differences between them help explain how SecY performs its distinctive function in the recognition and translocation of secretory proteins. The unified theory presented here explains the evolution of these features, and thus reconstructs a key step in the origin of cells.

Comparison of greater occipital nerve and supra orbital nerve blocks methods in the treatment of acute migraine attack: A randomized double-blind controlled trial.

OBJECTIVE: The main goal of this investigation is to compare the Greater Occipital Nerve (GON) and Supra Orbital Nerve (SON) block methods used in the treatment of migraine attacks in the ED with each other, in combination, and with a placebo. METHODS: This study was planned as a single center, prospective, double-blind, randomized control study. The patients were divided into 4 groups: GON, SON, Combined, and Placebo. Groups were named according to the nerve areas that were blocked. Therefore1% lidocaine for nerve blockade and 0.9% NaCl for placebo effect was used. Along with the time of admission, baseline pain scale values, as well as recordings at 30 and 60 min in addition to the Visual Analog Scale (VAS) at the 120th min. and Likert-Type (LT) Verbal scale at the 120th min. were measured. The primary outcome of this study was a change in the VAS and LT values at the 0-120th minute after treatment RESULTS: In this study, 128 patients in 4 groups were included in the analysis. In the GON group, SON group, and Combined group, the change observed at the 120th minute scores compared to baseline VAS scores was higher than Placebo group [OR (95% CI) = -17.4 (-24.8, -9.9), 32.1 (23.8, 40.3), 49.5 (41.9, 57), respectively]. In inter-group comparison, it was found that the VAS and LT scores of the Combined group and the GON group improved at a higher rate than the SON group CONCLUSIONS: SON blockade, GON blockade, and a combination of these two blockades are effective treatment methods in acute migraine attack. Performing a GON or Combined blockade for migraine attack causes greater pain reduction than SON blockade.

Moderate Traumatic Brain Injury Alters the Gastrointestinal Microbiome in a Time-Dependent Manner.

The microbiome is defined as the collective genomes of the microbes (composed of bacteria, bacteriophage, fungi, protozoa, and viruses) that colonize the human body, and alterations have been associated with a number of disease states. Changes in gut commensals can influence the neurologic system via the brain-gut axis, and systemic insults such as trauma or traumatic brain injury (TBI) may alter the gut microbiome. The objective of this study was to evaluate the gut microbiome in a preclinical TBI cortical impact model. Male rats underwent craniotomy and randomized to a sham group (n = 4), or a moderate TBI (n = 10) using a pneumatic impactor. MRI and behavioral assessments were performed pre-TBI and on days 2, 7, and 14 days thereafter. Microbiome composition was determined with 16s rRNA sequencing from fecal sample DNA pre-TBI and 2 hrs, 1, 3, and 7 days afterward. Alpha- and ß-bacterial diversity, as well as organizational taxonomic units (OTUs), were determined. Significant changes in the gut microbiome were evident as early as 2 h after TBI as compared with pre-injured samples and sham rats. While there were varying trends among the phylogenetic families across time, some changes persisted through 7 days in the absence of therapeutic intervention. While large structural lesions and behavioral deficits were apparent post-TBI, there were modest but significant decreases in α-diversity. Moreover, both changes in representative phyla and α-diversity measures were significantly correlated with MRI-determined lesion volume. These results suggest that changes in the microbiome may represent a novel biomarker to stage TBI severity and predict functional outcome.

Resection of the Primary Gastrointestinal Neuroendocrine Tumor Improves Survival With or Without Liver Treatment.

OBJECTIVE: The aim of this study was to determine outcomes of primary tumor resection in metastatic neuroendocrine tumors across all primary tumor sites. BACKGROUND: Primary tumor resection (PTR) may offer a survival benefit in metastatic gastrointestinal neuroendocrine tumors (GI-NETs); however, few studies have examined the effect of primary site and grade on resection and survival. METHODS: This is a retrospective study of patients with metastatic GI-NETs at presentation between 2005 and 2011 using the California Cancer Registry (CCR) dataset merged with California Office of Statewide Health Planning and Development (OSHPD) inpatient longitudinal database. Primary outcome was overall survival (OS). Univariate and multivariate (MV) analyses were performed using the Pearson Chi-squared tests and Cox proportional hazard, respectively. OS was estimated using the Kaplan-Meier method and log-rank test. RESULTS: A total of 854 patients with GI-NET metastases on presentation underwent 392 PTRs. Liver metastases occurred in 430 patients; 240 received liver treatment(s). PTR improved OS in patients with untreated metastases (median survival 10 vs 38 months, P < 0.001). On MV analysis adjusted for demographics, tumor stage, grade, chemotherapy use, Charlson comorbidity index, primary tumor location, or treatment of liver metastases, PTR with/without liver treatment improved OS in comparison to no treatment [hazard ratio (HR) 0.50, P < 0.001 and 0.39, P < 0.001, respectively]. PTR offered a survival benefit across all grades (low-grade, HR 0.38, P = 0.002 and high-grade, HR 0.62, P = 0.025) CONCLUSION:: PTR in GI-NET is associated with a better survival, with or without liver treatment, irrespective of grade. This study supports the resection of the primary tumor in patients with metastatic GI-NETs, independent of liver treatment.

Polytrauma independent of therapeutic intervention alters the gastrointestinal microbiome.

BACKGROUND: This study characterizes the gastrointestinal (GI) microbiome in a pre-clinical polytrauma hemorrhage model. METHODS: Rats (n = 6) were anesthetized, hemorrhaged 20% of their blood volume, and subjected to a femur fracture and crush injuries to the small intestine, liver, and limb skeletal muscle without resuscitation. Fecal samples were collected pre-injury and 2 h post-injury. Purified DNA from the samples underwent 16s rRNA sequencing for microbial quantification. Bacterial diversity analysis and taxonomic classification were performed. RESULTS: Following injury, the gut microbial composition was altered with a shift in beta diversity and significant differences in the relative abundance of taxa. The relative abundance of the families Lachnospiraceae and Mogibacteriaceae was increased at 2 h, while Barnesiellaceae and Bacteroidaceae were decreased. Alpha diversity was unchanged. CONCLUSIONS: The GI microbiome is altered in rats subjected to a polytrauma hemorrhage model at 2 h post-injury in the absence of antibiotics or therapeutic interventions.

Micrometer to 15 nm Printing of Metallic Inks with Fountain Pen Nanolithography.

The field of printed electronics is continually trying to reduce the dimensions of the electrical components. Here, a method of printing metallic lines with widths as small as 15 nm and up to a few micrometers using fountain pen nanolithography (FPN) is shown. The FPN technique is based on a bent nanopipette with atomic force feedback that acts similar to a nanopen. The geometry of the nanopen allows for rapid placement accuracy of the printing tip, on any desired location, with the highest of optical sub-micrometer resolution. Using this nanopen, investigations of various inks are undertaken together with instrumental and script-tool development that allows accurate printing of multiple layers. This has led to the printing of conductive lines using inks composed of silver nanoparticles and salt solutions of silver and copper. In addition, it is shown that the method can be applied to substrates of various materials with minimal effect on the dimension of the line. The line widths are varied by using nanopens with different orifices or by tailoring the wetting properties of the ink on the substrate. Metallic interconnections of conducting lines are reported.

Pancreatic Neuroendocrine Tumors: State-of-the-Art Diagnosis and Management.

The incidence of pancreatic neuroendocrine tumors (PNETs) has significantly increased in recent years, although this may reflect better detection and improved diagnosis, in addition to a true increase in incidence. The majority of PNETs are nonfunctional; up to half of nonmetastatic PNETs will present incidentally, and 85% will develop metastases over their lifetime. Treatment of PNETs is largely dictated by their heterogeneous nature and usually indolent behavior. Surgery is a mainstay of treatment, both in early PNETs and in metastatic disease. In this review, we focus on the treatment of well-differentiated early and metastatic PNETs, emphasizing current controversies, recent advances in therapy, and the multidisciplinary approach required for optimal treatment.

Live cell near-field optical imaging and voltage sensing with ultrasensitive force control.

Force controlled optical imaging of membranes of living cells is demonstrated. Such imaging has been extended to image membrane potential changes to demonstrate that live cell imaging has been achieved. To accomplish this advance, limitations inherent in atomic force microscopy (AFM) since its inception in 1986 [G. Binnig, C. F. Quate, and C. Gerber, "Atomic Force Microscope," Phys. Rev. Lett. 56, 930-933 (1986).] had to be overcome. The advances allow for live cell imaging of a whole genre of functional biological imaging with stiff (1-10N/m) scanned probe imaging cantilevers. Even topographic imaging of fine cell protrusions, such as microvilli, has been accomplished with such cantilevers. Similar topographic imaging has only recently been demonstrated with the standard soft (0.05N/m) cantilevers that are generally required for live cell imaging. The progress reported here demonstrates both ultrasensitive AFM (~100pN), capable of topographic imaging of even microvilli protruding from cell membranes and new functional applications that should have a significant impact on optical and other approaches in biological imaging of living systems and ultrasoft materials.

Minimally invasive distal pancreatectomy: greatest benefit for the frail.

OBJECTIVE: The benefits of minimally invasive distal pancreatectomy (MIDP) over open surgery continue to be investigated. Frailty is a known predictor of postoperative outcome. We hypothesized that the benefit of minimally invasive distal pancreatectomy is the greatest for the frailest of patients. METHODS: Data from the pancreas-targeted National Surgical Quality Improvement Program (NSQIP) database for 2014 were reviewed. A modified frailty index (mFI) with 11 preoperative variables previously validated for use in NSQIP was used to determine the correlation between frailty and postoperative outcomes, including Clavien grade IV complications. Patients were classified into non-frail (mFI = 0) or frail (mIF > 0), in which they were subclassified into mildly frail (mFI 1 or 2) or severely frail (mFI = 3). RESULTS: A total of 1,038 distal pancreatectomies (DP) were included in the analysis, of which 387 were minimally invasive (MIDP: laparoscopic: 285, robotic: 102), 558 open DP (ODP), and 93 MIDP converted to open (MIDPcODP: laparoscopic: 80, robotic: 13). More than 90% of patients had an mFI of 0 or 1 (mFI 0 = 473 (45.6%), 1 = 466 (44.9%), 2 = 94 (9.1%), and 3 = 5 (0.5%), respectively). Overall, 4.6% of patients experienced Clavien grade IV complications and 1.1% a mortality. Non-frail patients experienced a similar rate of grade IV Clavien complications with MIDP vs. ODP vs. MIDPcOP (2.3 vs. 2.3 vs. 4.9%; p = 0.6), whereas frail patients (mFI > 0) had a lower rate of complications with MIDP (2.4 vs. 8.3 vs. 11.5; p = 0.007). Worsening frailty correlated with an increase in complications (non-frail: 2.5%; mildly frail: 6.3%; severely frail: 20%; p = 0.005). CONCLUSION: MIDP is associated with a lower risk of Clavien grade IV complications compared to ODP for frail patients, especially for benign disease. Thus, minimally invasive approach may mitigate risk in frail patients.

Wireless Communication with Nanoplasmonic Data Carriers: Macroscale Propagation of Nanophotonic Plasmon Polaritons Probed by Near-Field Nanoimaging.

The ability to control the energy flow of light at the nanoscale is fundamental to modern communication and big-data technologies, as well as quantum information processing schemes. However, since photons are diffraction-limited, efforts of confining them to dimensions of integrated electronics have so far proven elusive. A promising way to facilitate nanoscale manipulation of light is through plasmon polaritons-coupled excitations of photons and charge carriers. These tightly confined hybrid waves can facilitate compression of optical functionalities to the nanoscale but suffer from huge propagation losses that limit their use to mostly subwavelength scale applications. With only weak evidence of macroscale plasmon polaritons, propagation has recently been reported theoretically and indirectly, no experiments so far have directly resolved long-range propagating optical plasmons in real space. Here, we launch and detect nanoscale optical signals, for record distances in a wireless link based on novel plasmonic nanotransceivers. We use a combination of scanning probe microscopies to provide high resolution real space images of the optical near fields and investigate their long-range propagation principles. We design our nanotransceivers based on a high-performance nanoantenna, Plantenna, hybridized with channel plasmon waveguides with a cross-section of 20 nm × 20 nm, and observe propagation for distances up to 1000 times greater than the plasmon wavelength. We experimentally show that our approach hugely outperforms both waveguide and wireless nanophotonic links. This successful alliance between Plantenna and plasmon waveguides paves the way for new generations of optical interconnects and expedites long-range interaction between quantum emitters and photomolecular devices.

Timing and severity of post-discharge morbidity after hepatectomy.

BACKGROUND: In order to decrease cost and increase healthcare quality there is an ongoing effort to reduce readmissions after complex operations. The timing and severity of post-discharge complications after hepatectomy need to be better defined. METHODS: All patients undergoing liver resection at a single institution from Jan 2009-Jun 2015 were included. Complications were scored using the comprehensive complication index (CCI). Multivariate analysis is performed using logistic regression. Receiver operating characteristics (ROCs) were analyzed to optimize the Readmission Risk Index (RRI). RESULTS: Of the 258 patients that met the inclusion criteria, 26 (10%) were readmitted within 30 days of discharge after hepatectomy. On multivariate analysis age ≥68 years (OR 3.76; 95% CI 1.47-9.63, p = 0.006), CCI ≥ 15 (OR 3.65; 95% CI 1.39-9.56, p = 0.008), maximum temperature within 48 h of discharge (OR 3.02; 95% CI 1.17-7.75, p = 0.022) and white blood cell count ≥10.2 billion cells/L within 48 h of discharge (OR 2.88; 95% CI 1.04-8, p = 0.043) were independent predictors of 30-day readmission. These variables were used to develop the RRI (ROC area 0.80; 95% CI 0.70-0.9, p < 0.001). CONCLUSION: The CCI and pre-discharge variables can help identify individuals at risk of readmission. Readmission risk reduction efforts should focus on this subset of patients.

Laparoscopy Can Safely Be Performed in Frail Patients Undergoing Colon Resection for Cancer.

The present study aims to evaluate the role of laparoscopy in frail patients undergoing colorectal surgery for colorectal cancer. A review of the 2011 to 2014 American College of Surgeons National Surgical Quality Improvement Program database was performed to identify frail patients (using a frailty index), who underwent resection for colorectal cancer. Univariable and multivariable analyses were performed to evaluate 30-day mortality and Clavien-Dindo grade IV (CD-IV) complications. A total of 52,087 patients with colorectal cancer were identified, of which frailty accounted for 2.63 per cent (index score ≥5). Patients above the age 85 were considered frail 6.8 per cent of the time and accounted for 24.5 per cent of patients with frailty. Laparoscopic surgery was performed in 32.9 and 53.1 per cent of patients with and without frailty (P < 0.001). Patients with frailty were less likely to die within 30 days of surgery if younger (P = 0.004), performed electively (P < 0.001), or laparoscopically (P < 0.001). On multivariate analysis, laparoscopy and elective surgery were associated with better perioperative survival; whereas, older age, male sex, and tobacco use were associated with 30-day mortality. Laparoscopy and lower body mass index were associated with fewer Clavien-Dindo grade IV complications. Although laparoscopy is performed less commonly in the frail, this study indicated better perioperative outcomes for patients undergoing elective surgery who were <85 years old.

Dermal γδ T-Cells Can Be Activated by Mitochondrial Damage-Associated Molecular Patterns.

BACKGROUND: Gamma delta T-cells have been shown to be important to the early immunoinflammatory response to injury, independent of infection. This unique T-cell population acts to regulate cell trafficking and the release of cytokines and growth factors. We propose this sterile inflammatory response is in part associated with damage associated molecular patterns (DAMPs) generated by major injury, such as burn, and mediated via toll-like receptors (TLRs). It is unknown whether DAMPs can activate resident γδ T-cells that reside in skin. METHODS: Gamma delta T-cells were isolated from the skin of male C57BL/6 mice by enzymatic digestion. Mitochondrial DAMPs (MTDs) were generated from mitochondria isolated from mouse livers by sonication and centrifugation. Dermal γδ T-cells were incubated with MTDs (0-500 µg/ml) for 24 hr and cells and supernatants were collected for analysis. RESULTS: MTDs activated dermal γδ T-cells, as evidenced by increased TLR2 and TLR4 expression following in vitro exposure. MTDs also induced the production of inflammatory cytokines (IL-1ß, IL-6), and growth factors (PDGF and VEGF) by γδ T-cells. CONCLUSIONS: These findings herein support the concept that MTDs released after tissue/cellular injury are capable of activating dermal γδ T-cells. We propose that the activation of this unique T-cell population is central in the initiation of sterile inflammation and also contributes to the subsequent healing processes.

The bright side of plasmonic gold nanoparticles; activation of Nrf2, the cellular protective pathway.

Plasmonic gold nanoparticles (AuNPs) are widely investigated for cancer therapy, due to their ability to strongly absorb light and convert it to heat and thus selectively destroy tumor cells. In this study we shed light on a new aspect of AuNPs and their plasmonic excitation, wherein they can provide anti-oxidant and anti-inflammatory protection by stimulating the cellular protective Nrf2 pathway. Our study was carried out on cells of the immune system, macrophages, and on skin cells, keratinocytes. A different response to AuNPs was noted in the two types of cells, explained by their distinct uptake profiles. In keratinocytes, the exposure to AuNPs, even at low concentrations, was sufficient to activate the Nrf2 pathway, without any irradiation, due to the presence of free AuNPs inside the cytosol. In contrast, in macrophages, the plasmonic excitation of the AuNPs by a low, non-lethal irradiation dose was required for their release from the constraining vesicles. The mechanism by which AuNPs activate the Nrf2 pathway was studied. Direct and indirect activation were suggested, based on the inherent ability of the AuNPs to react with thiol groups and to generate reactive oxygen species, in particular, under plasmonic excitation. The ability of AuNPs to directly activate the Nrf2 pathway renders them good candidates for treatment of disorders in which the up-regulation of Nrf2 is beneficial, specifically for topical treatment of inflammatory skin diseases.