Massive pancreatic serous cystadenomas raise important questions regarding surgical management of incidental pancreatic cystic lesions: a report of two cases.

Background: The widespread use of cross-sectional imaging and ultrasound has led to an increase in the diagnosis of pancreatic cystic neoplasms. These lesions have an estimated prevalence of 2.4% of which approximately 10-16% are serous cystadenoma (SCA). SCA is the most common benign pancreatic lesion; the vast majority are asymptomatic and associated with low risk for malignant transformation. Despite improved insight into the natural history of these tumors, recommendations for their management remain contentious. We present two cases of giant SCA that call attention to shortcomings of the current guidelines for management of benign cystic pancreatic lesions. Case Description: In both cases, patients presented for surgical evaluation late in the disease course despite multiple medical consultations with generalist and specialty providers. Although both lesions were resected, their late presentation may have increased risk for complication and post-operative morbidity. Conclusions: These cases highlight possible discrepancies between medical and surgical perspectives in the field and support future investigation into more aggressive surgical management of SCA.

Erratum to "Giant pedunculated hepatocellular adenoma masquerading as a subdiaphragmatic mass: Diagnostic challenges of a rare tumor" [Radiology Case Reports 16 (2021) 84-89].

[This corrects the article DOI: 10.1016/j.radcr.2020.10.047.].

Giant pedunculated hepatocellular adenoma masquerading as a subdiaphragmatic mass: Diagnostic challenges of a rare tumor.

Giant pedunculated hepatocellular adenomas are extremely rare tumors and often detected incidentally on cross-sectional imaging studies. We report the case of a 34-year-old woman who underwent cross-sectional imaging for staging evaluation of a uterine tumor. A large left subdiaphragmatic mass, without clear connection to the liver, was seen prompting diagnostic laparoscopy; during which a large pedunculated mass attached to the left lobe of the liver was found and resected. This case report highlights the challenges and pitfalls in the imaging diagnosis of pedunculated hepatocellular adenomas, such as difficulty in characterizing the mass or inability to identify the vascular attachment to the liver. Image-guided biopsy and diagnostic laparoscopy are valuable tools to establish diagnosis; most of these lesions are amenable to laparoscopic resection.

The Effect of Patient Education on the Perceptions of Resident Participation in Surgical Care.

OBJECTIVE: To decipher if patient attitudes toward resident participation in their surgical care can be improved with patient education regarding resident roles, education, and responsibilities. DESIGN: An anonymous questionnaire was created and distributed in outpatient surgery clinics that had residents involved with patient care. In total, 3 groups of patients were surveyed, a control group and 2 intervention groups. Each intervention group was given an informational pamphlet explaining the role, education, and responsibilities of residents. The first pamphlet used an analogy-based explanation. The second pamphlet used literature citations and statistics. SETTING: Keesler Medical Center, Keesler AFB, MS. University of Texas Health Science Center at San Antonio, San Antonio, TX. PARTICIPANTS: A total of 454 responses were collected and analyzed-211 in the control group, 118 in the analogy pamphlet group, and 125 in the statistics pamphlet group. RESULTS: Patients had favorable views of residents assisting with their surgical procedures, and the majority felt that outcomes were the same or better regardless of whether they read an informational pamphlet. Of all the patients surveyed, 80% agreed or strongly agreed that they expect to be asked permission for residents to be involved in their care. Further, 52% of patients in the control group agreed or strongly agreed to a fifth-year surgery resident operating on them independently for routine procedures compared to 62% and 65% of the patients who read the analogy pamphlet and statistics pamphlet, respectively (p = 0.05). When we combined the 2 intervention groups compared to the control group, this significant difference persisted (p = 0.02). CONCLUSION: Most patients welcome resident participation in their surgical care, but they expect to be asked permission for resident involvement. Patient education using an information pamphlet describing resident roles, education, and responsibilities improved patient willingness to allow a chief resident to operate independently.

Recent advances in optical fiber devices for microfluidics integration.

This paper examines the recent emergence of miniaturized optical fiber based sensing and actuating devices that have been successfully integrated into fluidic microchannels that are part of microfluidic and lab-on-chip systems. Fluidic microsystems possess the advantages of reduced sample volumes, faster and more sensitive biological assays, multi-sample and parallel analysis, and are seen as the de facto bioanalytical platform of the future. This paper considers the cases where the optical fiber is not merely used as a simple light guide delivering light across a microchannel, but where the fiber itself is engineered to create a new sensor or tool for use within the environment of the fluidic microchannel.

Preexposure Prophylaxis for HIV Infection Integrated With Municipal- and Community-Based Sexual Health Services.

IMPORTANCE: Several randomized clinical trials have demonstrated the efficacy of preexposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) acquisition. Little is known about adherence to the regimen, sexual practices, and overall effectiveness when PrEP is implemented in clinics that treat sexually transmitted infections (STIs) and community-based clinics serving men who have sex with men (MSM). OBJECTIVE: To assess PrEP adherence, sexual behaviors, and the incidence of STIs and HIV infection in a cohort of MSM and transgender women initiating PrEP in the United States. DESIGN, SETTING, AND PARTICIPANTS: Demonstration project conducted from October 1, 2012, through February 10, 2015 (last date of follow-up), among 557 MSM and transgender women in 2 STI clinics in San Francisco, California, and Miami, Florida, and a community health center in Washington, DC. Data were analyzed from December 18, 2014, through August 8, 2015. INTERVENTIONS: A combination of daily, oral tenofovir disoproxil fumarate and emtricitabine was provided free of charge for 48 weeks. All participants received HIV testing, brief client-centered counseling, and clinical monitoring. MAIN OUTCOMES AND MEASURES: Concentrations of tenofovir diphosphate in dried blood spot samples, self-reported numbers of anal sex partners and episodes of condomless receptive anal sex, and incidence of STI and HIV acquisition. RESULTS: Overall, 557 participants initiated PrEP, and 437 of these (78.5%) were retained through 48 weeks. Based on the findings from the 294 participants who underwent measurement of tenofovir diphosphate levels, 80.0% to 85.6% had protective levels (consistent with ≥4 doses/wk) at follow-up visits. African American participants (56.8% of visits; P = .003) and those from the Miami site (65.1% of visits; P < .001) were less likely to have protective levels, whereas those with stable housing (86.8%; P = .02) and those reporting at least 2 condomless anal sex partners in the past 3 months (88.6%; P = .01) were more likely to have protective levels. The mean number of anal sex partners declined during follow-up from 10.9 to 9.3, whereas the proportion engaging in condomless receptive anal sex remained stable at 65.5% to 65.6%. Overall STI incidence was high (90 per 100 person-years) but did not increase over time. Two individuals became HIV infected during follow-up (HIV incidence, 0.43 [95% CI, 0.05-1.54] infections per 100 person-years); both had tenofovir diphosphate levels consistent with fewer than 2 doses/wk at seroconversion. CONCLUSIONS AND RELEVANCE: The incidence of HIV acquisition was extremely low despite a high incidence of STIs in a large US PrEP demonstration project. Adherence was higher among those participants who reported more risk behaviors. Interventions that address racial and geographic disparities and housing instability may increase the impact of PrEP.

Transjugular Intrahepatic Portosystemic Shunt Flow Reduction with Adjustable Polytetrafluoroethylene-Covered Balloon-Expandable Stents Using the "Sheath Control" Technique.

PURPOSE: A complication of transjugular intrahepatic portosystemic shunts (TIPS) placement is refractory portosystemic encephalopathy (PSE) often requiring TIPS reduction. We report the results of a "sheath control technique" utilizing constraining sheaths during deployment of polytetrafluoroethylene (PTFE)-covered balloon-expandable stents, minimizing stent migration, and providing additional procedural control. METHODS: TIPS reduction was performed in 10 consecutive patients for PSE using Atrium iCast covered stents (Atrium Maquet Getinge Group, Germany). Within the indwelling TIPS stent, a 9 mm × 59 mm iCast stent was deployed with 2 cm exposed from the sheath's distal end and the majority of the stent within the sheath to create the distal hourglass shape. During balloon retraction, the stent was buttressed by the sheath. The proximal portion of the stent was angioplastied to complete the hourglass configuration, and the central portion of the stent was dilated to 5 mm. Demographics, pre- and post-procedure laboratory values, and outcomes were recorded. RESULTS: Ten patients underwent TIPS reduction with 100 % technical success. There was no stent migration during stent deployment. All patients experienced initial improvement of encephalopathy. One patient ultimately required complete TIPS occlusion for refractory PSE, and another developed TIPS occlusion 36 days post-procedure. There was no significant trend toward change in patients' MELD scores immediately post-procedure or at 30 days (p = 0.46, p = 0.47, respectively). CONCLUSION: TIPS reduction using Atrium iCast PTFE balloon-expandable stents using the "sheath control technique" is safe and effective, and minimizes the risk of stent migration.

Magnetic Resonance Imaging in Proximal Venous Outflow Obstruction.

BACKGROUND: Proximal venous outflow obstruction (PVOO) in the abdomen and pelvis is increasingly recognized as an important contributor to venous disease of the lower extremity. There are currently no guidelines regarding a noninvasive screening tool for PVOO, although magnetic resonance venography (MRV) is commonly used in many practices. The objective of this study was to determine the value and utility of MRV in diagnosis and screening for PVOO. METHODS: This retrospective study consisted of 46 consecutive patients, all of whom presented with signs and/or symptoms of PVOO and were evaluated with MRV followed by intravascular ultrasound (IVUS) and venography. Of these 46 patients suspected to have PVOO based on clinical evaluation, 24 patients had PVOO confirmed with IVUS and venography and PVOO was not observed on IVUS and venography in the remaining 22 patients. The MRV of these 46 patients was retrospectively reviewed in a blinded fashion and then correlated with IVUS and venography by 1 vascular surgeon. A scoring system was developed to define the types of radiography findings that were observed: normal, suspicious, and abnormal. RESULTS: When compared with IVUS and multiplane venography, the interpretation of MRV had a sensitivity of 100% and a specificity of 22.7%. The positive predictive value of MRV was 58.5%, and the negative predictive value was 100%. CONCLUSIONS: The high sensitivity (100%) and low specificity (22.7%) of MRV suggest that it can be a screening tool at best, used only to rule out PVOO; it cannot be used to confirm PVOO, given its a 41.5% false positive rate. Thus, the development of a different, noninvasive diagnostic test that can more accurately assess patients with suspected PVOO during the initial evaluation of their lower-extremity venous disease should be explored.

Single-mode fiber variable optical attenuator based on a ferrofluid shutter.

We report on the fabrication and characterization of a single-mode fiber variable optical attenuator (VOA) based on a ferrofluid shutter actuated by a magnetic field created by a low voltage electromagnet. We compare the performance of a VOA using oil-based ferrofluid, with one VOA using water-based 12 ferrofluid, and demonstrate broadband optical attenuation of up to 28 dB with polarization dependent 13 loss of 0.85 dB. Our optofluidic VOA has advantages over MEMS-based VOAs such as simple construction and the absence of mechanical moving parts.

High interest in preexposure prophylaxis among men who have sex with men at risk for HIV infection: baseline data from the US PrEP demonstration project.

BACKGROUND: Preexposure prophylaxis (PrEP) is the first biomedical intervention with proven efficacy to reduce HIV acquisition in men who have sex with men (MSM) and transgender women. Little is known about levels of interest and characteristics of individuals who elect to take PrEP in real-world clinical settings. METHODS: The US PrEP Demonstration Project is a prospective open-label cohort study assessing PrEP delivery in municipal sexually transmitted disease clinics in San Francisco and Miami and a community health center in Washington, DC. HIV-uninfected MSM and transgender women seeking sexual health services at participating clinics were assessed for eligibility and offered up to 48 weeks of emtricitabine/tenofovir for PrEP. Predictors of enrollment were assessed using a multivariable Poisson regression model, and characteristics of enrolled participants are described. RESULTS: Of 1069 clients assessed for participation, 921 were potentially eligible and 557 (60.5%) enrolled. In multivariable analyses, participants from Miami (adjusted Relative Risk [aRR]: 1.53; 95% confidence interval [CI]: 1.33 to 1.75) or DC (aRR: 1.33; 95% CI: 1.2 to 1.47), those who were self-referred (aRR: 1.48; 95% CI: 1.32 to 1.66), those with previous PrEP awareness (aRR: 1.56; 95% CI: 1.05 to 2.33), and those reporting >1 episode of anal sex with an HIV-infected partner in the last 12 months (aRR: 1.20; 95% CI: 1.09 to 1.33) were more likely to enroll. Almost all (98%) enrolled participants were MSM, and at baseline, 63.5% reported condomless receptive anal sex in the previous 3 months. CONCLUSIONS: Interest in PrEP is high among a diverse population of MSM at risk for HIV infection when offered in sexually transmitted disease and community health clinics.

A novel class of ion displacement ligands as antagonists of the αIIbß3 receptor that limit conformational reorganization of the receptor.

A collection of αIIbß3 integrin receptor antagonists possessing a unique MIDAS metal ion displacement mechanism of action is presented. Insight into these agents' structure-activity relationships, binding modality, and pharmacokinetic and pharmacodynamic profiles highlight the potential of these small molecule ion displacement ligands as attractive candidates for clinical development.

Incorporating a Mandatory Osteopathic Manipulative Medicine (OMM) curriculum in clinical clerkships: impact on student attitudes toward using OMM.

CONTEXT: As the osteopathic medical profession grows and enrollment in osteopathic graduate medical education falls, it is important to ensure that all osteopathic medical students receive adequate training in osteopathic manipulative medicine (OMM). OBJECTIVE: To determine if incorporating mandatory exposure to OMM into third- and fourth-year clinical clerkships favorably influences osteopathic medical students' comfort with the use of OMM. METHODS: All participants attended a 1-hour mandatory didactic lecture and a 3-hour practical clinic every week as part of their rotations at Wilson Memorial Medical Center. The authors distributed 2 hardcopy questionnaires to each subject: the first survey before rotations began and the second at the end of rotations. The survey comprised 7 clinical situations to which students used a visual analog scale ranging from "comfortable" to "uncomfortable" to describe their personal comfort with using OMM in each situation. Students' responses before and after rotations were compared using the paired t test. RESULTS: Sixty-eight students had rotations at the clinic; 50 students completed both questionnaires. The study demonstrated a statistically significant increase in comfort level of 17.9% (P<.001) after the rotations. CONCLUSIONS: Students' reported levels of comfort with OMM increased after they underwent formal OMM education. Incorporating exposure to an OMM curriculum may help instill a greater sense of identity as a future osteopathic physician and may influence participation in an osteopathic residency.

Novel disposable biochip platform employing supercritical angle fluorescence for enhanced fluorescence collection.

This paper presents an overview of development of a novel disposable plastic biochip for multiplexed clinical diagnostic applications. The disposable biochip is manufactured using a low-cost, rapid turn- around injection moulding process and consists of nine parabolic elements on a planar substrate. The optical elements are based on supercritical angle fluorescence (SAF) which provides substantial enhancement of the fluorescence collection efficiency but also confines the fluorescence detection volume strictly to the immediate proximity of the biochip surface, thereby having the potential to discriminate against background fluorescence from the analyte solution. An optical reader is also described that enables interrogation and fluorescence collection from the nine optical elements on the chip. The sensitivity of the system was determined with a biotin-avidin assay while its clinical utility was demonstrated in an assay for C-reactive protein (CRP), an inflammation marker.

Optical fiber-coupled ocular spectrometer for measurement of drug concentration in the anterior eye--applications in pharmaceuticals research.

This paper describes in detail a novel optoelectronic system designed to measure drug absorption in the anterior segment of the eye following topical application of drug formulations. This minimally invasive measurement technique offers both a method for determining drug concentration in human eyes, and demonstrates an alternative to current testing processes in model animals, which require paracentesis of the anterior chamber of the eye. The optoelectronic technique can be used with formulations, which possess appropriate spectral characteristics, namely unique absorption or fluorescence spectra. Preliminary experiments using our measurement system have been performed in rabbit and man, where we have been successful in achieving the direct measurement of topically applied brimonidine, an alpha-2 agonist used in the treatment of glaucoma. This demonstrates the feasibility of performing real-time, in vivo testing of ophthalmic drug formulations in the eye of human test subjects. We further demonstrate the novel application of the optoelectronic system for detection of topically applied UV-absorbing compounds in rabbit cadaver eyes, with a view to evaluating potential ocular sunscreen formulations. In summary, this method can be applied for the rapid comparison of the penetration of different drug formulations into the anterior eye at greatly reduced cost and time.

Effects of limiting extension at the alphaIIb genu on ligand binding to integrin alphaIIbbeta3.

Structural data of integrin alphaIIbbeta3 have been interpreted as supporting a model in which: 1) the receptor exists primarily in a "bent," low affinity conformation on unactivated platelets and 2) activation induces an extended, high affinity conformation prior to, or following, ligand binding. Previous studies found that "clasping" the alphaIIb head domain to the beta3 tail decreased fibrinogen binding. To study the role of alphaIIb extension about the genu, we introduced a disulfide "clamp" between the alphaIIb thigh and calf-1 domains. Clamped alphaIIbbeta3 had markedly reduced ability to bind the large soluble ligands fibrinogen and PAC-1 when activated with monoclonal antibody (mAb) PT25-2 but not when activated by Mn(2+) or by coexpressing the clamped alphaIIb with a beta3 subunit containing the activating mutation N339S. The clamp had little effect on the binding of the snake venom kistrin (M(r) 7,500) or alphaIIbbeta3-mediated adhesion to immobilized fibrinogen, but it did diminish the enhanced binding of mAb AP5 in the presence of kistrin. Collectively, our studies support a role for alphaIIb extension about the genu in the binding of ligands of 340,000 and 900,000 M(r) with mAb-induced activation but indicate that it is not an absolute requirement. Our data are consistent with alphaIIb extension resulting in increased access to the ligand-binding site and/or facilitating the conformational change(s) in beta3 that affect the intrinsic affinity of the binding pocket for ligand.

Structural and therapeutic insights from the species specificity and in vivo antithrombotic activity of a novel alphaIIb-specific alphaIIbbeta3 antagonist.

We previously reported on a novel compound (Compound 1; RUC-1) identified by high-throughput screening that inhibits human alphaIIbbeta3. RUC-1 did not inhibit alphaVbeta3, suggesting that it interacts with alphaIIb, and flexible ligand/rigid protein molecular docking studies supported this speculation. We have now studied RUC-1's effects on murine and rat platelets, which are less sensitive than human to inhibition by Arg-Gly-Asp (RGD) peptides due to differences in the alphaIIb sequences contributing to the binding pocket. We found that RUC-1 was much less potent in inhibiting aggregation of murine and rat platelets. Moreover, RUC-1 potently inhibited fibrinogen binding to murine platelets expressing a hybrid alphaIIbbeta3 receptor composed of human alphaIIb and murine beta3, but not a hybrid receptor composed of murine alphaIIb and human beta3. Molecular docking studies of RUC-1 were consistent with the functional data. In vivo studies of RUC-1 administered intraperitoneally at a dose of 26.5 mg/kg demonstrated antithrombotic effects in both ferric chloride carotid artery and laser-induced microvascular injury models in mice with hybrid halphaIIb/mbeta3 receptors. Collectively, these data support RUC-1's specificity for alphaIIb, provide new insights into the alphaIIb binding pocket, and establish RUC-1's antithrombotic effects in vivo.

Application of high-throughput screening to identify a novel alphaIIb-specific small- molecule inhibitor of alphaIIbbeta3-mediated platelet interaction with fibrinogen.

Small-molecule alphaIIbbeta3 antagonists competitively block ligand binding by spanning between the D224 in alphaIIb and the MIDAS metal ion in beta3. They variably induce conformational changes in the receptor, which may have undesirable consequences. To identify alphaIIbbeta3 antagonists with novel structures, we tested 33 264 small molecules for their ability to inhibit the adhesion of washed platelets to immobilized fibrinogen at 16 muM. A total of 102 compounds demonstrated 50% or more inhibition, and one of these (compound 1, 265 g/mol) inhibited ADP-induced platelet aggregation (IC(50): 13+/- 5 muM), the binding of soluble fibrinogen to platelets induced by mAb AP5, and the binding of soluble fibrinogen and a cyclic RGD peptide to purified alphaIIbbeta3. Compound 1 did not affect the function of GPIb, alpha2beta1, or the other beta3 family receptor alphaVbeta3. Molecular docking simulations suggest that compound 1 interacts with alphaIIb but not beta3. Compound 1 induced partial exposure of an alphaIIb ligand-induced binding site (LIBS), but did not induce exposure of 2 beta3 LIBS. Transient exposure of purified alphaIIbbeta3 to eptifibatide, but not compound 1, enhanced fibrinogen binding ("priming"). Compound 1 provides a prototype for small molecule selective inhibition of alphaIIbbeta3, without receptor priming, via targeting alphaIIb.