Laparoscopic-assisted ERCP following RYGB: a 12-year assessment of outcomes and learning curve at a high-volume pancreatobiliary center.

INTRODUCTION: Treatment of pancreaticobiliary pathology following Roux-en-Y gastric bypass (RYGB) poses significant technical challenges. Laparoscopic-assisted endoscopic retrograde cholangiopancreatography (LA-ERCP) can overcome those anatomical hurdles, allowing access to the papilla. Our aims were to analyze our 12-year institutional outcomes and determine the learning curve for LA-ERCP. METHODS: A retrospective review of cases between 2007 and 2019 at a high-volume pancreatobiliary unit was performed. Logistic regression was used to identify predictors of specific outcomes. To identify the learning curve, CUSUM analyses and innovative methods for standardizing the surgeon's timelines were performed. RESULTS: 131 patients underwent LA-ERCP (median age 60, 81% females) by 17 surgeons and 10 gastroenterologists. Cannulation of the papilla was achieved in all cases. Indications were choledocholithiasis (78%), Sphincter of Oddi dysfunction/Papillary stenosis (18%), management of bile leak (2%) and stenting/biopsy of malignant strictures (2%). Median total, surgical and ERCP times were 180, 128 and 48 min, respectively, and 47% underwent concomitant cholecystectomy. Surgical site infection developed in 9.2% and post-ERCP pancreatitis in 3.8%. Logistic regression revealed multiple abdominal operations and magnitude of BMI decrease (between RYGB and LA-ERCP) to be predictive of conversion to open approach. CUSUM analysis of operative time demonstrated a learning curve at case 27 for the surgical team and case 9 for the gastroenterology team. On binary cut analysis, 3-5 cases per surgeon were needed to optimize operative metrics. CONCLUSION: LA-ERCP is associated with high success rates and low adverse events. We identify outcome benchmarks and a learning curve for new adopters of this increasingly performed procedure.

'Black and white and every wrong colour': The medical history of Jane Austen and the possibility of systemic lupus erythematosus.

Jane Austen died 200 years ago at the age of 41 and authors have attributed her premature death to a wide variety of causes, which include Addison's disease and lymphoma.We have reviewed all of her available letters and extricated relevant medical information which reveal rheumatism, facial skin lesions, fever and marked fluctuation of these symptoms. The severity of these symptoms increased, leading to her death within a year.This range of clinical features fulfils the most recent classification criteria for systemic lupus erythematosus.

Loss aversion fails to replicate in the coronavirus pandemic: Evidence from an online experiment.

Loss aversion is a foundational bias and is a natural choice for interventions encouraging compliance during COVID-19. We compare the effectiveness of loss and gain messages and find no difference in the intention to comply with guidance or lockdown beliefs.

Phase Identification of the Layered Perovskite Ce xSr2- xMnO4 and Application for Solar Thermochemical Water Splitting.

Ruddlesden-Popper (layered perovskite) phases are attracting significant interest because of their unique potential for many applications requiring mixed ionic and electronic conductivity. Here we report a new, previously undiscovered layered perovskite of composition, Ce xSr2- xMnO4 ( x = 0.1, 0.2, and 0.3). Furthermore, we demonstrate that this new system is suitable for solar thermochemical hydrogen production (STCH). Synchrotron radiation X-ray diffraction and transmission electron microscopy are performed to characterize this new system. Density functional theory calculations of phase stability and oxygen vacancy formation energy (1.76, 2.24, and 2.66 eV/O atom, respectively with increasing Ce content) reinforce the potential of this phase for STCH application. Experimental hydrogen production results show that this materials system produces 2-3 times more hydrogen than the benchmark STCH oxide ceria at a reduction temperature of 1400 °C and an oxidation temperature of 1000 °C.

Auditory Streaming and Prediction in Tinnitus Sufferers.

OBJECTIVES: The aim of this study was to determine whether auditory streaming (segregation of incoming sounds into separate sound sources) and the ability to anticipate future auditory events are affected in tinnitus sufferers compared with nontinnitus controls with matched levels of hearing. It was hypothesized that tinnitus would result in abnormal electroencephalography responses to tone deviants and tone omissions compared to controls for frequencies near the pitch of tinnitus, and this should correspond with increased levels of cortical γ and θ oscillatory rhythms. DESIGN: Sixteen individuals with tinnitus (10 men and 6 women; age, 53.44; SD, 12.92 years) and 14 control participants (8 men and 6 women; age, 50.25; SD, 18.54 years) took part in the study. A modified version of the ABA streaming paradigm, with repeating triplet pattern of two frequencies (A and B) presented as A-B-A, was used to examine deviant-related prediction error. Omission-related prediction errors were examined using a modified version of a tone-omission paradigm. Regions of interest were frontocentral, left frontal, right frontal, and temporal lobes. RESULTS: A larger N1c waveform was elicited in the absence of any tone deviation within the left primary auditory cortex of tinnitus participants. No differences were present between groups for omissions. The only difference in oscillatory band activity between the two groups in this study was in response to tones 7 semitones different from tinnitus pitch, with significantly lower ß-2 band activity present for the tinnitus group, correlating most with activity within the right inferior occipital gyrus. CONCLUSIONS: The findings from this study imply that cortical-level auditory stream segregation is altered among individuals with tinnitus.

The Influence of Ambulatory Aid on Lower-Extremity Muscle Activation During Gait.

CONTEXT: Foot and ankle injuries are common and often require a nonweight-bearing period of immobilization for the involved leg. This nonweight-bearing period usually results in muscle atrophy for the involved leg. There is a dearth of objective data describing muscle activation for different ambulatory aids that are used during the aforementioned nonweight-bearing period. OBJECTIVE: To compare activation amplitudes for 4 leg muscles during (1) able-bodied gait and (2) ambulation involving 3 different ambulatory aids that can be used during the acute phase of foot and ankle injury care. DESIGN: Within-subject, repeated measures. SETTING: University biomechanics laboratory. PARTICIPANTS: Sixteen able-bodied individuals (7 females and 9 males). INTERVENTION: Each participant performed able-bodied gait and ambulation using 3 different ambulatory aids (traditional axillary crutches, knee scooter, and a novel lower-leg prosthesis). MAIN OUTCOME MEASURE: Muscle activation amplitude quantified via mean surface electromyography amplitude throughout the stance phase of ambulation. RESULTS: Numerous statistical differences (P < .05) existed for muscle activation amplitude between the 4 observed muscles, 3 ambulatory aids, and able-bodied gait. For the involved leg, comparing the 3 ambulatory aids: (1) knee scooter ambulation resulted in the greatest vastus lateralis activation, (2) ambulation using the novel prosthesis and traditional crutches resulted in greater biceps femoris activation than knee scooter ambulation, and (3) ambulation using the novel prosthesis resulted in the greatest gastrocnemius activation (P < .05). Generally speaking, muscle activation amplitudes were most similar to able-bodied gait when subjects were ambulating using the knee scooter or novel prosthesis. CONCLUSIONS: Type of ambulatory aid influences muscle activation amplitude. Traditional axillary crutches appear to be less likely to mitigate muscle atrophy during the nonweighting, immobilization period that often follows foot or ankle injuries. Researchers and clinicians should consider these results when recommending ambulatory aids for foot or ankle injuries.

Provision of social norm feedback to high prescribers of antibiotics in general practice: a pragmatic national randomised controlled trial.

BACKGROUND: Unnecessary antibiotic prescribing contributes to antimicrobial resistance. In this trial, we aimed to reduce unnecessary prescriptions of antibiotics by general practitioners (GPs) in England. METHODS: In this randomised, 2 × 2 factorial trial, publicly available databases were used to identify GP practices whose prescribing rate for antibiotics was in the top 20% for their National Health Service (NHS) Local Area Team. Eligible practices were randomly assigned (1:1) into two groups by computer-generated allocation sequence, stratified by NHS Local Area Team. Participants, but not investigators, were blinded to group assignment. On Sept 29, 2014, every GP in the feedback intervention group was sent a letter from England's Chief Medical Officer and a leaflet on antibiotics for use with patients. The letter stated that the practice was prescribing antibiotics at a higher rate than 80% of practices in its NHS Local Area Team. GPs in the control group received no communication. The sample was re-randomised into two groups, and in December, 2014, GP practices were either sent patient-focused information that promoted reduced use of antibiotics or received no communication. The primary outcome measure was the rate of antibiotic items dispensed per 1000 weighted population, controlling for past prescribing. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN32349954, and has been completed. FINDINGS: Between Sept 8 and Sept 26, 2014, we recruited and assigned 1581 GP practices to feedback intervention (n=791) or control (n=790) groups. Letters were sent to 3227 GPs in the intervention group. Between October, 2014, and March, 2015, the rate of antibiotic items dispensed per 1000 population was 126.98 (95% CI 125.68-128.27) in the feedback intervention group and 131.25 (130.33-132.16) in the control group, a difference of 4.27 (3.3%; incidence rate ratio [IRR] 0.967 [95% CI 0.957-0.977]; p<0.0001), representing an estimated 73,406 fewer antibiotic items dispensed. In December, 2014, GP practices were re-assigned to patient-focused intervention (n=777) or control (n=804) groups. The patient-focused intervention did not significantly affect the primary outcome measure between December, 2014, and March, 2015 (antibiotic items dispensed per 1000 population: 135.00 [95% CI 133.77-136.22] in the patient-focused intervention group and 133.98 [133.06-134.90] in the control group; IRR for difference between groups 1.01, 95% CI 1.00-1.02; p=0.105). INTERPRETATION: Social norm feedback from a high-profile messenger can substantially reduce antibiotic prescribing at low cost and at national scale; this outcome makes it a worthwhile addition to antimicrobial stewardship programmes. FUNDING: Public Health England.

Tryptophan to Arginine Substitution in Puroindoline-b Alters Binding to Model Eukaryotic Membrane.

We have studied how puroindoline-b (PINB) mutants bind to model eukaryotic membranes dependent on binary composition of anionic:zwitterionic phospholipids and the presence of cholesterol and sphingomyelin in the model membrane. We have found that the trends in lipid binding behavior are different for wild-type PINB compared to its naturally occurring PINB(Trp44Arg) mutant form and have seen evidence of protein-induced domain formation within the lipid layer structure. Results show that selective binding of antimicrobial peptides to different membrane types is as a result of differences in lipid composition and the arrangement of lipids within the membrane surface. However, membrane-binding behavior is not easily predicted; it is determined by net charge, hydrophobicity, and the amphiphilicity of the protein/peptide lipid-binding domain.

Comparative stability of Major Facilitator Superfamily transport proteins.

Membrane transporters are a vital class of proteins for which there is little available structural and thermodynamic information. The Major Facilitator Superfamily (MFS) is a large group of transport proteins responsible for transporting a wide range of substrates in eukaryotes and prokaryotes. We have used far-UV circular dichroism (CD) to assess whether transporters from this superfamily have the same chemical and thermal stability. We have compared the stability of five different MFS transporters; PepTSo from Shewanella oneidensis and LacY, GalP, GlpT and XylE from Escherichia coli, as well as a known stable mutant of LacY, LacY-C154G. CD stability measurements revealed that these transporters fall into two broad categories. The 'urea-sensitive' category includes LacY-WT, GalP and GlpT, which each lose around a third of their secondary structure in 8 M urea and two-thirds in the harsher denaturant guanidine hydrochloride (GuHCl). The 'urea-resistant' category includes LacY-C154G, XylE and PepTSo. These resistant transporters lose very little secondary structure in 8 M urea, and LacY-C154G and PepTSo resist denaturation by GuHCl up to a concentration of 4 M. The stabilities of LacY, GlpT, XylE and PepTSo correlated with their crystal structure conformations, implying that a similar conformation is adopted in vitro. The 'urea-sensitive' transporters LacY and GlpT were crystallised inward-open states, while XylE and PepTSo were crystallised in occluded states. This study highlights the importance of studying a wide range of similar proteins, as a similar secondary structure and overall function does not necessarily confer the same stability in vitro.

The accuracy and reliability of an app-based audiometer using consumer headphones: pure tone audiometry in a normal hearing group.

OBJECTIVE: To undertake a preliminary evaluation of the test-retest reliability, and accuracy of an iPad audiometer app using commercial earphones as a low-cost alternative to a clinical audiometer in a restricted sample of normal hearing participants. DESIGN: Twenty participants self-reporting normal hearing undertook four pure-tone audiometry tests in a single session. Two tests were performed with a 2-channel Type 1 audiometer (GSI-61) using EAR insert earphones and two tests with an iPad based app (Audiogram Mobile) using Apple earbud headphones. STUDY SAMPLE: Twenty normal hearing participants (13 female and seven male participants, aged 21-26 years) were recruited for the test-retest and accuracy evaluations. RESULTS: The app resulted in different thresholds to the audiometer (F(1, 19) = 16.635, p < 0.001). However test-retest reliability was similar. The app froze or quit unexpectedly over 25% of times used. CONCLUSIONS: Audiometer apps have great potential for clinical settings, especially in resource scarce environments, but reliability should not be assumed. While a low cost-alternative to standard transducers, issues of accuracy and calibration of consumer headphones need to be addressed before such combinations can be used with confidence.

Role of Lipid Composition on the Interaction between a Tryptophan-Rich Protein and Model Bacterial Membranes.

The interaction between tryptophan-rich puroindoline proteins and model bacterial membranes at the air-liquid interface has been investigated by FTIR spectroscopy, surface pressure measurements, and Brewster angle microscopy. The role of different lipid constituents on the interactions between lipid membrane and protein was studied using wild type (Pin-b) and mutant (Trp44 to Arg44 mutant, Pin-bs) puroindoline proteins. The results show differences in the lipid selectivity of the two proteins in terms of preferential binding to specific lipid head groups in mixed lipid systems. Pin-b wild type was able to penetrate mixed layers of phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) head groups more deeply compared to the mutant Pin-bs. Increasing saturation of the lipid tails increased penetration and adsorption of Pin-b wild type, but again the response of the mutant form differed. The results provide insight as to the role of membrane architecture, lipid composition, and fluidity on antimicrobial activity of proteins. Data show distinct differences in the lipid binding behavior of Pin-b as a result of a single residue mutation, highlighting the importance of hydrophobic and charged amino acids in antimicrobial protein and peptide activity.

Anchored p90 ribosomal S6 kinase 3 is required for cardiac myocyte hypertrophy.

RATIONALE: Cardiac myocyte hypertrophy is the main compensatory response to chronic stress on the heart. p90 ribosomal S6 kinase (RSK) family members are effectors for extracellular signal-regulated kinases that induce myocyte growth. Although increased RSK activity has been observed in stressed myocytes, the functions of individual RSK family members have remained poorly defined, despite being potential therapeutic targets for cardiac disease. OBJECTIVE: To demonstrate that type 3 RSK (RSK3) is required for cardiac myocyte hypertrophy. METHODS AND RESULTS: RSK3 contains a unique N-terminal domain that is not conserved in other RSK family members. We show that this domain mediates the regulated binding of RSK3 to the muscle A-kinase anchoring protein scaffold, defining a novel kinase anchoring event. Disruption of both RSK3 expression using RNA interference and RSK3 anchoring using a competing muscle A-kinase anchoring protein peptide inhibited the hypertrophy of cultured myocytes. In vivo, RSK3 gene deletion in the mouse attenuated the concentric myocyte hypertrophy induced by pressure overload and catecholamine infusion. CONCLUSIONS: Taken together, these data demonstrate that anchored RSK3 transduces signals that modulate pathologic myocyte growth. Targeting of signaling complexes that contain select kinase isoforms should provide an approach for the specific inhibition of cardiac myocyte hypertrophy and for the development of novel strategies for the prevention and treatment of heart failure.

Small duodenal carcinoids: a case series comparing endoscopic resection and autoamputation with band ligation.

GOALS: We sought to compare the efficacy and safety of endoscopic ultrasound-guided endoscopic resection (ER) and endoscopic band ligation (EBL) for autoamputation of small duodenal carcinoids. BACKGROUND: The ideal management of small duodenal carcinoid tumors remains unclear. STUDY: A retrospective review of duodenal carcinoids over a 10-year period (2002 to 2012) was performed at our tertiary-care teaching hospital. All patients with duodenal carcinoids ≤10 mm in size treated with either ER or EBL were included. The main outcome measurements were the efficacy and safety of endotherapy. RESULTS: A total of 37 patients with 39 subcentimeter duodenal carcinoids were identified. In the EBL group, the mean (SD) tumor size was 6.7±2.1 mm compared with 6.7±1.7 mm in the ER group (P=0.943). The mean Ki-67 index was ≤2% in specimens available for histologic analysis in both groups (16/23 EBL and 15/16 ER). The positive deep margin rate in the ER group was 68.8%. Residual carcinoid tumor cells were detected on follow-up biopsies in 1 patient after EBL, and 2 patients after ER. All underwent subsequent successful endotherapy. No adverse events occurred in the EBL group compared with an 18.8% adverse event rate in the ER group (P=0.066). CONCLUSIONS: Endoscopic ultrasound-guided EBL is a safe, effective method for removal of small superficial duodenal carcinoids and seems to be a lower risk alternative to conventional ER with cautery.

A microRNA-based test improves endoscopic ultrasound-guided cytologic diagnosis of pancreatic cancer.

BACKGROUND & AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in combination with cytopathology is the optimal method for diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) and other pancreatic lesions. Its clinical utility, however, can be limited by high rates of indeterminate or false-negative results. We aimed to develop and validate a microRNA (miRNA)-based test to improve preoperative detection of PDAC. METHODS: Levels of miRNAs were analyzed in a centralized clinical laboratory by relative quantitative polymerase chain reaction in 95 formalin-fixed paraffin-embedded specimens and 228 samples collected by EUS-FNA during routine evaluations of patients with solid pancreatic masses at 4 institutions in the United States, 1 in Canada, and 1 in Poland. RESULTS: We developed a 5-miRNA expression classifier, consisting of MIR24, MIR130B, MIR135B, MIR148A, and MIR196, that could identify PDAC in well-characterized, formalin-fixed, paraffin-embedded specimens. Detection of PDAC in EUS-FNA samples increased from 78.8% by cytology analysis alone (95% confidence interval, 72.2%-84.5%) to 90.8% when combined with miRNA analysis (95% confidence interval, 85.6%-94.5%). The miRNA classifier correctly identified 22 additional true PDAC cases among 39 samples initially classified as benign, indeterminate, or nondiagnostic by cytology. Cytology and miRNA test results each were associated significantly with PDAC (P < .001), with positive predictive values greater than 99% (95% confidence interval, 96%-100%). CONCLUSIONS: We developed and validated a 5-miRNA classifier that can accurately predict which preoperative pancreatic EUS-FNA specimens contain PDAC. This test might aid in the diagnosis of pancreatic cancer by reducing the number of FNAs without a definitive adenocarcinoma diagnosis, thereby reducing the number of repeat EUS-FNA procedures.

Long-term safety and impact of immune recovery in heavily treatment-experienced adults receiving fostemsavir for up to 5 years in the phase 3 BRIGHTE study.

Introduction: Fostemsavir is a gp120-directed attachment inhibitor approved for heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. We provide detailed week 240 safety results from the BRIGHTE study and evaluate the impact of immune recovery on safety outcomes. Methods: The phase 3 BRIGHTE trial is ongoing; data for this analysis were collected from the first participant's first visit (February 23, 2015) through the last participant's last visit for week 240 (March 22, 2021). Safety endpoints were assessed in participants who received fostemsavir + optimized background therapy. In participants with baseline CD4+ T-cell count <200 cells/mm3, exposure-adjusted adverse event (AE) rates were assessed among subgroups with or without CD4+ T-cell count ≥200 cells/mm3 at any time during 48-week analysis periods through week 192. Results: Through a median of 258 weeks (range, 0.14-319) of treatment, discontinuations due to AEs occurred in 30/371 (8%) participants. Serious AEs were reported in 177/371 (48%) participants, including 16 drug-related events in 13 (4%) participants. Thirty-five (9%) deaths occurred, primarily related to AIDS or acute infections. COVID-19-related events occurred in 25 (7%) participants; all resolved without sequelae. Among participants with baseline CD4+ T-cell count <200 cells/mm3, 122/162 (75%) achieved CD4+ T-cell count ≥200 cells/mm3 at week 192. Exposure-adjusted AE rates were markedly lower among participants achieving CD4+ T-cell count ≥200 cells/mm3 at any time vs those sustaining <200 cells/mm3. No new AIDS-defining events were reported after week 48 in participants with CD4+ T-cell count ≥200 cells/mm3. Conclusions: Cumulative safety findings through the BRIGHTE 240-week interim analysis are consistent with other trials in HTE participants with advanced HIV-1 and comorbid disease. Reduced rates of AIDS-defining events and AEs were observed in participants with immunologic recovery on fostemsavir-based treatment. Clinical trial number: NCT02362503, https://clinicaltrials.gov/study/NCT02362503.

p90 ribosomal S6 kinase 3 contributes to cardiac insufficiency in α-tropomyosin Glu180Gly transgenic mice.

Myocardial interstitial fibrosis is an important contributor to the development of heart failure. Type 3 p90 ribosomal S6 kinase (RSK3) was recently shown to be required for concentric myocyte hypertrophy under in vivo pathological conditions. However, the role of RSK family members in myocardial fibrosis remains uninvestigated. Transgenic expression of α-tropomyosin containing a Glu180Gly mutation (TM180) in mice of a mixed C57BL/6:FVB/N background induces a cardiomyopathy characterized by a small left ventricle, interstitial fibrosis, and diminished systolic and diastolic function. Using this mouse model, we now show that RSK3 is required for the induction of interstitial fibrosis in vivo. TM180 transgenic mice were crossed to RSK3 constitutive knockout (RSK3(-/-)) mice. Although RSK3 knockout did not affect myocyte growth, the decreased cardiac function and mild pulmonary edema associated with the TM180 transgene were attenuated by RSK3 knockout. The improved cardiac function was consistent with reduced interstitial fibrosis in the TM180;RSK3(-/-) mice as shown by histology and gene expression analysis, including the decreased expression of collagens. The specific inhibition of RSK3 should be considered as a potential novel therapeutic strategy for improving cardiac function and the prevention of sudden cardiac death in diseases in which interstitial fibrosis contributes to the development of heart failure.

Endoscopic therapy is effective for patients with chronic pancreatitis.

BACKGROUND & AIMS: Endoscopic therapy (ET) frequently is used to treat patients with painful chronic pancreatitis (CP), but little is known about outcomes of patients for whom ET was not successful who then underwent surgery, or outcomes after ET compared with only medical treatment. We evaluated use and long-term effectiveness of ET in a well-defined cohort of patients with CP. METHODS: We analyzed data from 146 patients with CP who participated in the North American Pancreatitis Study 2 at the University of Pittsburgh Medical Center from 2000 to 2006; 71 (49%) patients received ET at the University of Pittsburgh Medical Center. Success of ET and surgery were defined by cessation of narcotic therapy and resolution of episodes of acute pancreatitis. Disease progression was followed up from its onset until January 1, 2011 (mean, 8.2 ± 4.7 y). RESULTS: Patients who underwent ET had more symptoms (pain, recurrent pancreatitis) and had more complex pancreatic morphology (based on imaging) than patients who received medical therapy. ET had a high rate of technical success (60 of 71 cases; 85%); its rates of clinical success were 51% for 28 of 55 patients for whom follow-up data were available (mean time, 4.8 ± 3.0 y) and 50% for 12 of 24 patients who underwent surgery after receiving ET. Patients who responded to ET were significantly older, had a shorter duration of disease before ET, had less constant pain, and required fewer daily narcotics than patients who did not respond to ET. Among the 36 symptomatic patients who received medical therapy and were followed up for a mean period of 5.7 ± 4.1 years, 31% improved and 53% had no change in symptoms; of these, 21% underwent surgery. CONCLUSIONS: ET is clinically successful for 50% of patients with symptomatic CP. When ET is not successful, surgery has successful outcomes in 50% of patients. Symptoms resolve in 31% of symptomatic patients who receive only medical therapy.

The role of protein hydrophobicity in thionin-phospholipid interactions: a comparison of α1 and α2-purothionin adsorbed anionic phospholipid monolayers.

The plant defence proteins α1- and α2-purothionin (Pth) are type 1 thionins from common wheat (Triticum aestivum). These highly homologous proteins possess characteristics common amongst antimicrobial peptides and proteins, that is, cationic charge, amphiphilicity and hydrophobicity. Both α1- and α2-Pth possess the same net charge, but differ in relative hydrophobicity as determined by C18 reversed phase HPLC. Brewster angle microscopy, X-ray and neutron reflectometry, external reflection FTIR and associated surface pressure measurements demonstrated that α1 and α2-Pth interact strongly with condensed phase 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) monolayers at the air/liquid interface. Both thionins disrupted the in-plane structure of the anionic phospholipid monolayers, removing lipid during this process and both penetrated the lipid monolayer in addition to adsorbing as a single protein layer to the lipid head-group. However, analysis of the interfacial structures revealed that the α2-Pth showed faster disruption of the lipid film and removed more phospholipid (12%) from the interface than α1-Pth. Correlating the protein properties and lipid binding activity suggests that hydrophobicity plays a key role in the membrane lipid removal activity of thionins.

Intraprocedural tissue diagnosis during ERCP employing a new cytology preparation of forceps biopsy (Smash protocol).

OBJECTIVES: Techniques of tissue sampling at endoscopic retrograde cholangiopancreatography (ERCP) have been underutilized due to technical demands, low yield, and lack of immediate intraprocedural diagnosis. The objective of this study was to describe a new inexpensive, highly efficient ERCP tissue processing, and interpretation technique to address these issues. METHODS: A retrospective, institutional review board approved, single-center study was done at a tertiary-care medical center. Between June 2004 and February 2009, 133 patients (age 38-95 years; men 53%) with suspicious biliary strictures underwent ERCP with tissue sampling using a new technique. Small forceps biopsy specimens were forcefully smashed between two dry glass slides, immediately fixed, stained with rapid Papanicolaou, and interpreted by an on-site pathologist during the procedure (Smash protocol). RESULTS: Of the 117 proven to have cancer, true-positive Smash preps included pancreatic cancer 49/66 (74%), cholangiocarcinoma 23/29 (79%), metastatic cancer 8/15 (53%), and other 4/7 (57%). The median number of Smash biopsies to diagnosis was 3 (range 1-17). Suspicious or atypical results were considered to be negative in this study. There were no false positives and no complications. Smash had an overall sensitivity of 89/117 (76%) for all cases. The true-positive yield of immediate Smash prep cytology, combined with ERCP fine needle aspirate (FNA) and forceps biopsy histology was 77/95 (81%) for primary pancreaticobiliary cancers. CONCLUSIONS: Immediate cytopathologic diagnosis at ERCP was established in 72% of patients presenting with suspected malignant biliary obstruction using a new cytological preparation of forceps biopsies. This approach to ERCP tissue sampling permits immediate diagnosis and avoids the need for subsequent procedures, adds little cost and time, and is safe to perform.