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Small extracellular vesicles (sEVs) play a central role in cell-to-cell communication in normal physiology and in disease, including gestational diabetes mellitus (GDM). The goal of the present study was to test the hypothesis that chronic administration of sEVs isolated from GDM causes glucose intolerance in healthy pregnant mice. Small EVs were isolated from plasma between 24 and 28 weeks gestation from healthy pregnant women (controls) and GDM, and infused intravenously for 4 days in late pregnant mice using a mini-osmotic pump. Subsequently in vivo glucose tolerance was assessed, and muscle and adipose tissue insulin sensitivity and islet glucose stimulated insulin secretion (GSIS) were determined in vitro. Mice infused with sEVs from GDM developed glucose intolerance. Administration of sEVs from controls, but not sEVs from GDM women, stimulated islet GSIS and increased fasting insulin levels in pregnant mice. Neither infusion of sEVs from controls nor from GDM women affected muscle insulin sensitivity, placental insulin or mTOR signaling, placental and fetal weight. Moreover, these results were not associated with immunomodulatory effects as human sEVs did not activate mouse T cells in vitro. We suggest that circulating sEVs regulate maternal glucose homeostasis in pregnancy and may contribute to the attenuated islet insulin secretion and more pronounced glucose intolerance in GDM as compared with healthy pregnancy. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 65-year-old man who had various symptoms and medical history that required further investigation. The patient's social context, including his country of origin and migration history, was highlighted as an important factor in the diagnostic process. The differential diagnosis included several possibilities, such as lymphoma, myeloid neoplasm, and tuberculosis. Ultimately, the patient was diagnosed with extranodal NK/T-cell lymphoma and latent tuberculosis. The article emphasizes the significance of considering a patient's social history and geographic exposures in clinical reasoning, while avoiding the conflation of race with biology and pathology. [Extracted from the article]

Aim: This study assessed the effectiveness of blended essential oils on menstrual cramps for outpatients with primary dysmenorrhea and explored the analgesic ingredients in the essential oils. Material and Methods: A randomized, double-blind clinical trial was conducted. Forty-eight outpatients were diagnosed with primary dysmenorrhea by a gynecologist and had 10-point numeric rating scales that were more than 5. The patients were randomly assigned to an essential oil group ( n = 24) and a synthetic fragrance group ( n = 24). Essential oils blended with lavender ( Lavandula officinalis), clary sage ( Salvia sclarea) and marjoram ( Origanum majorana) in a 2:1:1 ratio was diluted in unscented cream at 3% concentration for the essential oil group. All outpatients used the cream daily to massage their lower abdomen from the end of the last menstruation continuing to the beginning of the next menstruation. Results: Both the numeric rating scale and the verbal rating scale significantly decreased ( P < 0.001) after one menstrual cycle intervention in the two groups. The duration of pain was significantly reduced from 2.4 to 1.8 days after aromatherapy intervention in the essential oil group. Conclusion: Aromatic oil massage provided relief for outpatients with primary dysmenorrhea and reduced the duration of menstrual pain in the essential oil group. The blended essential oils contain four key analgesic components that amount to as much as 79.29%; these analgesic constitutes are linalyl acetate, linalool, eucalyptol, and β-caryophyllene. This study suggests that this blended formula can serve as a reference for alternative and complementary medicine on primary dysmenorrhea. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is a serious public health issue affecting 9-15% of all pregnancies worldwide. Recently, it has been suggested that extracellular vesicles (EVs) play a role throughout gestation, including mediating a placental response to hyperglycaemia. Here, we investigated the EV-associated miRNA profile across gestation in GDM, assessed their utility in developing accurate, multivariate classification models, and determined the signaling pathways in skeletal muscle proteome associated with the changes in the EV miRNA profile.Methods: Discovery: A retrospective, case-control study design was used to identify EV-associated miRNAs that vary across pregnancy and clinical status (i.e. GDM or Normal Glucose Tolerance, NGT). EVs were isolated from maternal plasma obtained at early, mid and late gestation (n = 29) and small RNA sequencing was performed. Validation: A longitudinal study design was used to quantify expression of selected miRNAs. EV miRNAs were quantified by real-time PCR (cases = 8, control = 14, samples at three times during pregnancy) and their individual and combined classification efficiencies were evaluated. Quantitative, data-independent acquisition mass spectrometry was use to establish the protein profile in skeletal muscle biopsies from normal and GDM.Results: A total of 2822 miRNAs were analyzed using a small RNA library, and a total of 563 miRNAs that significantly changed (p < 0.05) across gestation and 101 miRNAs were significantly changed between NGT and GDM. Analysis of the miRNA changes in NGT and GDM separately identified a total of 256 (NGT-group), and 302 (GDM-group) miRNAs that change across gestation. A multivariate classification model was developed, based on the quantitative expression of EV-associated miRNAs, and the accuracy to correctly assign samples was > 90%. We identified a set of proteins in skeletal muscle biopsies from women with GDM associated with JAK-STAT signaling which could be targeted by the miRNA-92a-3p within circulating EVs. Interestingly, overexpression of miRNA-92a-3p in primary skeletal muscle cells increase insulin-stimulated glucose uptake.Conclusions: During early pregnancy, differently-expressed, EV-associated miRNAs may be of clinical utility in identifying presymptomatic women who will subsequently develop GDM later in gestation. We suggest that miRNA-92a-3p within EVs might be a protected mechanism to increase skeletal muscle insulin sensitivity in GDM. [ABSTRACT FROM AUTHOR]

Background: Caveolae proteins play diverse roles in cancer development and progression. In prostate cancer, non‐caveolar caveolin‐1 (CAV1) promotes metastasis, while CAVIN1 attenuates CAV1‐induced metastasis. Here, we unveil a novel mechanism linking CAV1 to selective loading of exosomes with metastasis‐promoting microRNAs. Results: We identify hnRNPK as a CAV1‐regulated microRNA binding protein. In the absence of CAVIN1, non‐caveolar CAV1 drives localisation of hnRPNK to multi‐vesicular bodies (MVBs), recruiting AsUGnA motif‐containing miRNAs and causing their release within exosomes. This process is dependent on the lipid environment of membranes as shown by cholesterol depletion using methyl‐β‐cyclodextrin or by treatment with n‐3 polyunsaturated fatty acids. Consistent with a role in bone metastasis, knockdown of hnRNPK in prostate cancer PC3 cells abolished the ability of PC3 extracellular vesicles (EV) to induce osteoclastogenesis, and biofluid EV hnRNPK is elevated in metastatic prostate and colorectal cancer. Conclusions: Taken together, these results support a novel pan‐cancer mechanism for CAV1‐driven exosomal release of hnRNPK and associated miRNA in metastasis, which is modulated by the membrane lipid environment. [ABSTRACT FROM AUTHOR]

To determine the incidence of clinically significant adverse events after long-term, fixed-dose, generic highly active antiretroviral therapy (HAART) use among HIV-infected individuals in South India, we examined the experiences of 3154 HIV-infected individuals who received a minimum of 3 months of generic HAART between February 1996 and December 2006 at a tertiary HIV care referral center in South India. The most common regimens were 3TC + d4T + nevirapine (NVP) (54.8%), zidovudine (AZT) + 3TC + NVP (14.5%), 3TC + d4T + efavirenz (EFV) (20.1%), and AZT + 3TC + EFV (5.4%). The most common adverse events and median CD4 at time of event were rash (15.2%; CD4, 285 cells/ μL) and peripheral neuropathy (9.0% and 348 cells/ μL). Clinically significant anemia (hemoglobin <7 g/dL) was observed in 5.4% of patients (CD4, 165 cells/ μL) and hepatitis (clinical jaundice with alanine aminotransferase > 5 times upper limits of normal) in 3.5% of patients (CD4, 260 cells/ μL). Women were significantly more likely to experience lactic acidosis, while men were significantly more likely to experience immune reconstitution syndrome ( p < 0.05). Among the patients with 1 year of follow-up, NVP therapy was significantly associated with developing rash and d4T therapy with developing peripheral neuropathy ( p < 0.05). Anemia and hepatitis often occur within 12 weeks of initiating generic HAART. Frequent and early monitoring for these toxicities is warranted in developing countries where generic HAART is increasingly available. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) function as natural mediators of intercellular communication, secreted by cells to facilitate cell-cell signaling. Due to their low toxicity, immunogenicity, biodegradability, and potential to encapsulate therapeutic drugs, EVs hold significant therapeutic promise. Nevertheless, their limited targeting ability often diminishes their therapeutic impact. Therefore, enhancing EVs by incorporating targeting units onto their membranes could bolster their targeting capabilities, enabling them to accumulate in specific cells and tissues. In this study, we engineered EVs to fuse ephrin-B2 with the EV membrane protein LAMP2b. This modification aimed to direct the engineered EVs toward the ephrin-B4 receptor expressed on the surface of ovarian cancer cells. The engineered EVs retained their inherent properties, including size, expression of EV membrane proteins, and morphology, upon isolation. In vitro experiments using real-time imaging revealed that EVs engineered with the ephrin-B2 ligand exhibited substantial internalization and uptake by ovarian cancer cells, in stark contrast to native EVs. In vivo, the engineered EVs carrying the ephrin-B2 ligand effectively targeted ovarian cancer cells, surpassing the targeting efficiency of control EVs. This innovative approach establishes a novel targeting system, enhancing the uptake of EVs by ovarian cancer cells. Our findings underscore the potential of using EVs to target cancer cells, thereby enhancing the effectiveness of anti-cancer therapies while minimizing off-target effects and toxicity in normal cells and organs., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: In response to a decline in bedside procedures performed by hospitalists, some hospital medicine groups have created medical procedure services (MPSs) concentrating procedures under the expertise of trained hospitalist-proceduralists., Objectives: To characterize the structure, breadth, and heterogeneity of academic medical center MPSs, as well as compare the procedural landscape for groups with and without an MPS., Methods: The Survey of Internal Medicine Providers' Limitations and Experiences with Procedures and MPSs, is a cross-sectional study, conducted in the United States and Canada through a web-based survey administered from October 2022 to March 2023. We used convenience and snowball sampling to identify eligible study participants. The survey explored presence of MPS, procedure volumes, patient safety, and educational practices. For MPSs, we explored onboarding, staffing, skill maintenancy, funding, and barriers to growth., Results: Forty instututions (response rate 97.5%), represented by members of the Procedural Research and Innovation for Medical Educators (PRIME) consortum participated in the survey. MPSs were found in 75% of the surveyed institutions. Most MPSs (97%) involved trainees and were staffed by internists (100%) who often had additional clinical duties (70%). The majority (83%) of MPSs used checklists and procedural safety guidelines, but only 53% had a standardized process for tracking complications. There was significant variability in determining procedural competency and supervising trainees. Groups with an MPS reported higher procedure volume compared to those without., Conclusions: MPSs were highly prevalent among the participating instutitions, offered a broad array of bedside procedures, and often included trainees. There was a high variability in funding models, procedure volumes, patient safety practices, and skill maintenance requirements., (© 2024 Society of Hospital Medicine.)

Pleural effusions are categorized as transudative or exudative, with transudative effusions usually reflecting the sequala of a systemic etiology and exudative effusions usually resulting from a process localized to the pleura. Common causes of transudative pleural effusions include congestive heart failure, cirrhosis, and renal failure, whereas exudative effusions are typically due to infection, malignancy, or autoimmune disorders. This document summarizes appropriateness guidelines for imaging in four common clinical scenarios in patients with known or suspected pleural effusion or pleural disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Extracellular vesicles (EVs), including exosomes, have significant potential for diagnostic and therapeutic applications. The lack of standardized methods for efficient and high-throughput isolation and analysis of EVs, however, has limited their widespread use in clinical practice. Surface epitope immunoaffinity (SEI) isolation utilizes affinity ligands, including antibodies, aptamers, or lectins, that target specific surface proteins present on EVs. Paramagnetic bead-SEI isolation represents a fit-for-purpose solution for the reproducible, high-throughput isolation of EVs from biofluids and downstream analysis of RNA, protein, and lipid biomarkers that is compatible with clinical laboratory workflows. This study evaluates a new SEI isolation method for enriching subpopulations of EVs. EVs were isolated from human plasma using a bead-based SEI method designed for on-bead and downstream analysis of EV-associated RNA and protein biomarkers. Western blot analysis confirmed the presence of EV markers in the captured nanoparticles. Mass spectrometry analysis of the SEI lysate identified over 1500 proteins, with the top 100 including known EV-associated proteins. microRNA (miRNA) sequencing followed by RT-qPCR analysis identified EV-associated miRNA transcripts. Using SEI, EVs were isolated using automated high-throughput particle moving instruments, demonstrating equal or higher protein and miRNA yield and recovery compared to manual processing. SEI is a rapid, efficient, and high-throughput method for isolating enriched populations of EVs; effectively reducing contamination and enabling the isolation of a specific subpopulation of EVs. In this study, high-throughput EV isolation and RNA extraction have been successfully implemented. This technology holds great promise for advancing the field of EV research and facilitating their application for biomarker discovery and clinical research., (© The Author(s) 2024. Published by Oxford University Press.)

Extracellular vesicles (EVs) are nanosized biomolecular packages involved in intercellular communication. EVs are released by all cells, making them broadly applicable as therapeutic, diagnostic, and mechanistic components in (patho)physiology. Sample purity is critical for correctly attributing observed effects to EVs and for maximizing therapeutic and diagnostic performance. Lipoprotein contaminants represent a major challenge for sample purity. Lipoproteins are approximately six orders of magnitude more abundant in the blood circulation and overlap in size, shape, and density with EVs. This study represents the first example of an EV purification method based on the chemically-induced breakdown of lipoproteins. Specifically, a styrene-maleic acid (SMA) copolymer is used to selectively breakdown lipoproteins, enabling subsequent size-based separation of the breakdown products from plasma EVs. The use of the polymer followed by tangential flow filtration or size-exclusion chromatography results in improved EV yield, preservation of EV morphology, increased EV markers, and reduced contaminant markers. SMA-based EV purification enables improved fluorescent labeling, reduces interactions with macrophages, and enhances accuracy, sensitivity, and specificity to detect EV biomarkers, indicating benefits for various downstream applications. In conclusion, SMA is a simple and effective method to improve the purity and yield of plasma-derived EVs, which favorably impacts downstream applications., (© 2023 The Authors. Small published by Wiley‐VCH GmbH.)

Placental extracellular vesicles (EVs) can be found in the maternal circulation throughout gestation, and their concentration, content and bioactivity are associated with pregnancy outcomes, including gestational diabetes mellitus (GDM). However, the effect of changes in the maternal microenvironment on the mechanisms associated with the secretion of EVs from placental cells remains to be fully established. Here, we evaluated the effect of high glucose on proteins associated with the trafficking and release of different populations of EVs from placental cells. BeWo and HTR8/SVneo cells were used as placental models and cultured under 5-mM D-glucose (i.e. control) or 25-mM D-glucose (high glucose). Cell-conditioned media (CCM) and cell lysate were collected after 48 h. Different populations of EVs were isolated from CCM by ultracentrifugation (i.e. pellet 2K-g, pellet 10K-g, and pellet 100K-g) and characterised by Nanoparticle Tracking Analysis. Quantitative proteomic analysis (IDA/SWATH) and multiple reaction monitoring protocols at high resolution (MRM HR ) were developed to quantify 37 proteins related to biogenesis, trafficking/release and recognition/uptake of EVs. High glucose increased the secretion of total EVs across the pellets from BeWo cells, an effect driven mainly by changes in the small EVs concentration in the CCM. Interestingly, no effect of high glucose on HTR8/SVneo cells EVs secretion was observed. High glucose induces changes in proteins associated with vesicle trafficking in BeWo cells, including Heat Shock Protein Family A (Hsp70) Member 9 (HSPA9) and Member 8 (HSPA8). For HTR8/SVneo, altered proteins including prostaglandin F2α receptor regulatory protein (FPRP), RAB5A, RAB35, RAB5B, and RB11B, STAM1 and TSG101. These proteins are associated with the secretion and trafficking of EVs, which could explain in part, changes in the levels of circulating EVs in diabetic pregnancies. Further, we identified that proteins RAB11B, PDCD6IP, STAM, HSPA9, HSPA8, SDCBP, RAB5B, RAB5A, RAB7A and ERAP1 regulate EV release in response to high and low glucose when overexpressed in cells. Interestingly, immunohistochemistry analysis of RAB7A revealed distinct changes in placental tissues obtained from women with normal glucose tolerance (NGT, n  = 6) and those with GDM ( n  = 6), influenced by diet or insulin treatment. High glucose regulation of proteins involved in intercellular dynamics and the trafficking of multivesicular bodies to the plasma membrane in placental cells is relevant in the context of GDM pregnancies., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Background: Traditional cardiac rehabilitation (CR) improves cardiovascular outcomes and reduces mortality, but less is known about the relative benefit of intensive CR (ICR) which incorporates greater lifestyle education through 72 sessions (versus 36 in CR). Our objective was to determine whether ICR is associated with a mortality and cardiovascular benefit compared with CR., Methods: Retrospective cohort study of Medicare Fee-For-Service beneficiaries in a 100% sample, claims data set. Qualifying events were captured from May 1, 2016 to December 31, 2019 and ICR/CR utilization captured from May 1, 2016 to December 31, 2020. Among patients attending at least 1 day of either CR or ICR, Cox proportional hazards models using a 1 to 5 propensity score match were used to compare utilization and the association of ICR versus CR participation with (1) all-cause mortality and (2) cardiovascular-related hospitalizations or nonfatal cardiac events. Dose-response was assessed by the number of days attended., Results: From 2016 to 2019, 1 277 358 unique patients met at least one qualifying indication for ICR/CR from 2016 to 2019. Of these, 262 579 (20.6%) and 4452 (0.4%) attended at least one session of CR or ICR, respectively (mean [SD] age, 73.2 [7.8] years; 32.3% female). In the matched sample, including 26 659 total patients (median, 2.4-year follow-up), ICR was associated with 12% lower all-cause mortality (multivariable adjusted hazard ratio, 0.88 [95% CI, 0.78-0.99]; P =0.036) compared with CR but no significant difference for cardiovascular-related hospitalization or nonfatal cardiac events. The mortality benefit was seen for both ICR and CR per day strata, with each modality demonstrating a clear dose-response benefit., Conclusions: ICR is associated with lower mortality than traditional CR among Medicare beneficiaries but no difference in cardiovascular-related hospitalization or nonfatal cardiac events. Moreover, ICR and CR demonstrate a dose-response relationship for mortality. Additional studies are needed to confirm these observations and to better understand the mechanisms by which ICR may lead to a reduction in mortality., Competing Interests: Disclosures Dr Husaini received research support from Pritikin intensive cardiac rehabilitation (ICR), LLC through the Foundation for Barnes-Jewish Hospital and has received honoraria from Bristol Meyers Squibb. Dr Racette receives research support from the National Institutes of Health (NIH; R01 AG070717, R01 AG060499, R61 HL155858, R34 HL158947, R33 AG070455, R25 HL105400), and the Foundation for Barnes-Jewish Hospital. Dr Rich receives support from the NIH (R01 AG060499, R01 AG078153, R01 HL147862, R01 HL151431). Dr Joynt Maddox receives research support from the National Heart, Lung, and Blood Institute (R01HL143421 and R01HL164561), National Institute of Nursing research (U01NR020555), and National Institute on Aging (R01AG060935, R01AG063759, and R21AG065526), and from Humana. She also serves on the Health Policy Advisory Council for the Centene Corporation (St Louis, MO). Dr Peterson has stock holdings in Medtronic, Johnson and Johnson and receives research support from the NIH (R61/R33 HL155858, R01 AG060499-01, R01 HL 165238), the American Heart Association (No. 23SCISA1145192), the Children’s Discovery Institute, the Clinical and Translational Research Funding Program (CTRFP), and the Foundation for Barnes-Jewish Hospital in Saint Louis, MO. The other authors report no conflicts.

Extracellular vesicles (EVs) are messengers that carry information in the form of proteins, lipids, and nucleic acids and are not only essential for intercellular communication but also play a critical role in the progression of various pathologies, including ovarian cancer. There has been recent substantial research characterising EV cargo, specifically, the lipid profile of EVs. Lipids are involved in formation and cargo sorting of EVs, their release and cellular uptake. Numerous lipidomic studies demonstrated the enrichment of specific classes of lipids in EVs derived from cancer cells suggesting that the EV associated lipids can potentially be employed as minimally invasive biomarkers for early diagnosis of various malignancies, including ovarian cancer. In this review, we aim to provide a general overview of the heterogeneity of EV, biogenesis, their lipid content, and function in cancer progression focussing on ovarian cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The objective of this work is to compare our outcomes using thulium laser enucleation of prostate (ThuLEP) to the single-port robot-assisted simple prostatectomy (SP RASP) in the surgical management of benign prostatic hyperplasia (BPH)., Methods: A retrospective cohort study was conducted from January 2017 through December 2021 of men who underwent SP RASP and ThuLEP performed by a single surgeon with an enucleation experience of >300 cases and extensive robotic experience. The primary outcome was changed in International Prostate Symptom Score (IPSS) postoperatively. Secondary outcomes were operative time, length of stay (LOS), change in post-void residuals (PVR), de novo stress- or urge-urinary incontinence (SUI, UUI), and rate of complications., Results: One hundred two patients underwent surgery during the study period: 33 RASP and 69 ThuLEP. There was no difference in preoperative characteristics, including age and body mass index, between both groups. Changes in IPSS scores postoperatively were not significant between SP RASP versus ThuLEP (-17 vs. -14, p  = 0.2956). SP RASP had a longer operative time (180 vs. 90 min, p  < 0.0001). There was no difference in LOS (0 vs. 0 days, p  = 0.2904). There was no difference in change in PVR (-96 vs. -91 mL, p  = 0.8504). SP RASP patients had significantly less postoperative SUI than ThuLEP (0 vs. 13 patients, p  = 0.0083), while there was no difference in UUI between both groups (4 vs. 2 patients, p  = 0.0843). There was no difference in 30-day complication rate (21.2% vs. 21.7%, p  = 0.9517), although there were three ThuLEP patients with Clavien-Dindo Class III or higher complication., Conclusions: There was no difference in change in IPSS scores between the two groups. ThuLEP is associated with shorter postoperative catheter days and decreased operative times. Hospital LOS was equivalent. SP RASP demonstrates significantly improved continence rates. Though SP RASP is within the initial learning curve at our institution, early results demonstrate the role for this modality alongside ThuLEP in the treatment of large gland BPH., Competing Interests: Dr. Simone Crivellaro is a consultant for Intuitive Surgical, Inc. All other authors have nothing to disclose., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Introduction: Gender dysphoria affects over 1 million American adults. Vaginoplasty is a critical step in gender affirmation, and many patients have insufficient genital skin for full-depth penile inversion vaginoplasty (PIV). We reviewed the literature for technical considerations addressing this and present our data supporting the use of peritoneal flaps (Davydov technique)., Materials and Methods: A comprehensive review of modern literature was conducted. Second, we present a retrospective case review of our experience with PIV, including data from procedures utilizing peritoneal flaps., Results: We identified 20 original articles, including retrospective and prospective case and cohort studies. Approaches included the application of local soft tissue grafts and flaps, peritoneal flaps, and intestinal segments. Between June 2018 and February 2021, 47 patients at our institution, underwent PIV for the treatment of gender dysphoria. Nineteen of those patients underwent robotic-assisted peritoneal flap procedure in addition to PIV. In this cohort, the mean follow-up was 200.6 ± 124.8 days. Mean neovaginal depth was 13.1 ± 3.0 cm intra-operatively and 11.0 cm at the last follow-up. Twenty-six percent of complications were Clavien Grade 1 or 2; others included wound dehiscence (30.4%), perianal and urethral fistula (13.0%), and neovaginal stenosis (8.7%). The majority of patients reported satisfactory results in terms of sexual function with intact tactile and erogenous sensation. Almost half were able to have penetrative vaginal intercourse at the last follow-up. We did not aim to perform statistical calculations to compare the outcomes of PIV with and without robotic-assisted peritoneal flap augmentation, as the groups were not constructed in that manner. However, it is evident that anatomical and functional results as well as the distribution of postoperative complications seem similar., Conclusion: Vaginoplasty is indicated in a growing population of patients with a wide range of medical histories and anatomic variations. Genitourinary reconstructive surgeons must have several methods to achieve full-depth vaginoplasty in cases of inadequate genital skin. Peritoneal flaps serve as a versatile, safe, and functionally advantageous solution., (© 2022 Wiley Periodicals LLC.)

Introduction: The World Professional Association for Transgender Health has recently updated its Standards of Care (SOC) clinical guidelines for the transgender and gender diverse (TGD) population. This article aims to outline the 2012 SOC for surgical management of TGD people and describe the changes to the surgical management guidelines in this year's update., Methods and Results: The surgical management guidelines between the 7th and 8th SOC were compared and contrasted. The 8th SCO included language that broadened surgical interventions and emphasized the new responsibilities of surgeons. Major changes include reducing the number of letters of referral by a mental health provider to one for those choosing to undergo surgical treatment., Conclusions: The latest surgical management guidelines for the TGD population emphasizes a holistic approach utilizing a multidisciplinary team in both pre- and postoperative settings., (© 2022 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Objective: To evaluate the efficacy and safety of robot-assisted laparoscopic pyeloplasty (RALP) and describe the short and long-term outcomes of pediatric RALP., Methods: We retrospectively reviewed all patients ..±21 years old who underwent primary RALP from 7/2007 through 12/2019. Patients were excluded from postoperative analysis if follow-up data after stent removal was not available. The primary outcome was surgical success, defined as radiographic improvement of hydronephrosis without need for reoperation. Secondary outcomes were time to reoperation and 90-day complication rate., Results: A total of 356 patients underwent primary repair of ureteropelvic junction obstruction during the study period; 29.ßpatients were limited to intraoperative data due to lack of follow-up imaging. Radiographic improvement at latest follow-up was seen in 308/327 (94.2%). Ten of 327 patients (3.1%) underwent reoperation: 7 were identified within 1 year of RALP and 3 were identified over 1 year after RALP. The median time to reoperation was 13.0 months (IQR 9.3-21.7). We defined long-term as>3 years after pyeloplasty. Over one-third (122/327, 37.3%) of the cohort had>3 years of follow-up, none of whom developed evidence of recurrent obstruction requiring reoperation beyond 3 years. Complications occurred within 90 days of surgery in 20/327 (6.1%)., Conclusion: This largest single-institution series confirms short- and long-term surgical effectiveness and safety of RALP. Our data also indicate that most patients who needed reoperation were identified within 1 year, and reoperation more than 3 years after RALP is rare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Advancements in extracellular vesicle (EV) studies necessitate the development of optimized storage conditions to ensure preservation of physical and biochemical characteristics. In this study, the most common buffer for EV storage (phosphate-buffered saline/PBS) was compared to a cryoprotective 5% sucrose solution. The size distribution and concentration of EVs from two different sources changed to a greater extent after -80 °C storage in PBS compared to the sucrose solution. Additionally, molecular surface protrusions and transmembrane proteins were more prevalent in EVs stored in the sucrose solution compared to those stored in PBS. This study demonstrates, for the first time, that distinct ring-like molecular complexes and cristae-like folded membranous structures are visible upon EV degradation. Taken together, the size, concentration, molecular surface extensions, and transmembrane proteins of EVs varied substantially based on the buffer used for -80 °C storage, suggesting that biocompatible cryoprotectants, such as sucrose, should be considered for EV studies., Competing Interests: Competing Interests The authors declare that they have no competing interests.

Pulmonary hypertension may be idiopathic or related to a large variety of diseases. Various imaging examinations may be helpful in diagnosing and determining the etiology of pulmonary hypertension. Imaging examinations discussed in this document include chest radiography, ultrasound echocardiography, ventilation/perfusion scintigraphy, CT, MRI, right heart catheterization, and pulmonary angiography. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer-reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer-reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

This document provides recommendations regarding the role of imaging in the staging and follow-up of esophageal cancer. For initial clinical staging, locoregional extent and nodal disease are typically assessed with esophagogastroduodenoscopy and esophageal ultrasound. FDG-PET/CT or CT of the chest and abdomen is usually appropriate for use in initial clinical staging as they provide additional information regarding distant nodal and metastatic disease. The detection of metastatic disease is critical in the initial evaluation of patients with esophageal cancer because it will direct patients to a treatment pathway centered on palliative radiation rather than surgery. For imaging during treatment, particularly neoadjuvant chemotherapy, FDG-PET/CT is usually appropriate, because some studies have found that it can provide information regarding primary lesion response, but more importantly it can be used to detect metastases that have developed since the induction of treatment. For patients who have completed treatment, FDG-PET/CT or CT of the chest and abdomen is usually appropriate for evaluating the presence and extent of metastases in patients with no suspected or known recurrence and in those with a suspected or known recurrence. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

The da Vinci single-port (SP) system (Intuitive Surgical, Sunnyvale, CA) is the newest robotic platform released and approved for use in the urologist's armimentarium. This article (and complementary video) aims to summarize the most common problems that have been encountered at the University of Illinois at Chicago when using the SP system. Moreover, solutions to these issues will be presented.

Problem Definition: Performance feedback, in which clinicians are given data on select metrics, is widely used in the context of quality improvement. However, there is a lack of practical guidance describing the process of developing performance feedback systems., Initial Approach: This study took place at the University of California, San Francisco (UCSF) with hospitalist physicians. Participatory design methodology was used to develop a performance dashboard and feedback system. Twenty hospitalist physicians participated in a series of six design sessions and two surveys. Each design session and survey systematically addressed key components of the feedback system, including design, metric selection, data delivery, and incentives. The Capability Opportunity Motivation and Behavior (COM-B) model was then used to identify behavior change interventions to facilitate engagement with the dashboard during a pilot implementation., Key Insights, Lessons Learned: In regard to performance improvement, physicians preferred collaboration over competition and internal motivation over external incentives. Physicians preferred that the dashboard be used as a tool to aid in clinical practice improvement and not punitively by leadership. Metrics that were clinical or patient-centered were perceived as more meaningful and more likely to motivate behavior change., Next Steps: The performance dashboard has been introduced to the entire hospitalist group, and evaluation of implementation continues by monitoring engagement and physician attitudes. This will be followed by targeted feedback interventions to attempt to improve performance., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Extracellular vesicles (EVs) carry a wide range of molecules, such as proteins, RNAs, and DNA. EVs are secreted from a wide range of cells, including placental cells. Interestingly, EVs secreted from placental cells have been identified in maternal circulation as early as 6 weeks of gestation, and their concentration increases with the gestational age. While there is growing interest in elucidating the role of exosomes during normal and complicated pregnancies, progress in the field has been delayed because of the inability to quantify placental EVs from the maternal circulation. Recent reports have demonstrated the presence of placental-type alkaline phosphatase (PLAP) EVs only in the blood of pregnant women, indicating that PLAP is a marker to identify EVs secreted from the placenta. Therefore, here we describe a workflow to quantify placental EVs from maternal circulation using a targeted proteomics approach based on selecting specific peptides identified in the PLAP protein., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Proton pump inhibitors (PPIs) are often prescribed beyond their medically-approved duration of use. Long-term PPI use has been linked with numerous adverse effects and contributes to polypharmacy. This study sought to understand the effect of evidence-based education to resident and faculty physicians on deprescribing inappropriate PPIs. We hypothesized that this educational intervention would result in fewer inappropriate PPI prescriptions., Methods: We performed a chart review on all adult patients in a family medicine residency program practice, identifying those inappropriately taking PPIs. All physicians in the practice participated in an educational intervention regarding deprescribing inappropriate PPIs and were given frequent reminders to continue their deprescribing efforts. We reviewed charts at the end of the study to identify patients with successful deprescribing attempts., Results: Of the 187 patients prescribed inappropriate PPIs in the study, 100 remained on PPIs at the end of the study (46.6% success rate). There was a significant decrease in the number of patients inappropriately prescribed PPIs by each physician over the course of the study, from a mean of 17.0 (beginning) to 9.1 (end)., Conclusion: Physician education with reminders is an effective means of reducing the number of inappropriate PPIs prescribed in a family medicine residency practice. Future studies could investigate the effectiveness of educational interventions with other medication classes that are often prescribed inappropriately., (© 2021 by the Society of Teachers of Family Medicine.)

Hypoxia is a key regulator of cancer progression and chemoresistance. Ambiguity remains about how cancer cells adapt to hypoxic microenvironments and transfer oncogenic factors to surrounding cells. In this study, we determined the effects of hypoxia on the bioactivity of sEVs in a panel of ovarian cancer (OvCar) cell lines. The data obtained demonstrate a varying degree of platinum resistance induced in OvCar cells when exposed to low oxygen tension (1% oxygen). Using quantitative mass spectrometry (Sequential Window Acquisition of All Theoretical Fragment Ion Mass Spectra, SWATH) and targeted multiple reaction monitoring (MRM), we identified a suite of proteins associated with glycolysis that change under hypoxic conditions in cells and sEVs. Interestingly, we identified a differential response to hypoxia in the OvCar cell lines and their secreted sEVs, highlighting the cells' heterogeneity. Proteins are involved in metabolic reprogramming such as glycolysis, including putative hexokinase (HK), UDP-glucuronosyltransferase 1-6 (UD16), and 6-phosphogluconolactonase (6 PGL), and their presence correlates with the induction of platinum resistance. Furthermore, when normoxic cells were exposed to sEVs from hypoxic cells, platinum-resistance increased significantly ( p < 0.05). Altered chemoresistance was associated with changes in glycolysis and fatty acid synthesis. Finally, sEVs isolated from a clinical cohort ( n = 31) were also found to be enriched in glycolysis-pathway proteins, especially in patients with recurrent disease. These data support the hypothesis that hypoxia induces changes in sEVs composition and bioactivity that confers carboplatin resistance on target cells. Furthermore, we propose that the expression of sEV-associated glycolysis-pathway proteins is predictive of ovarian cancer recurrence and is of clinical utility in disease management.

Syphilis has many atypical morphologies which can present a diagnostic challenge, especially in patients with HIV/AIDS who may have multiple concurrent conditions. We describe a 41-year-old man with recently diagnosed HIV who was admitted for acute right vision loss and a diffuse rash with involvement of the palms and soles. He received diagnoses of secondary syphilis and Kaposi sarcoma in the setting of AIDS. Examination revealed an unusual dark brown-to-purple umbilicated papule with a necrotic center on the abdomen, raising a diagnostic dilemma. Skin biopsy showed secondary syphilis, despite the concurrent diagnosis of Kaposi sarcoma. The patient was treated with antibiotic and antiretroviral therapy and symptoms resolved. This case aims to share the clinical reasoning behind diagnosing a patient with HIV/AIDS with multiple concurrent conditions and to raise awareness of the many atypical cutaneous manifestations of secondary syphilis.

Preeclampsia (PE) is associated with long-term morbidity in mothers and lifelong morbidities for their children, ranging from cerebral palsy and cognitive delay in preterm infants, to hypertension, diabetes and obesity in adolescents and young adults. There are several processes that are critical for development of materno-fetal exchange, including establishing adequate perfusion of the placenta by maternal blood, and the formation of the placental villous vascular tree. Recent studies provide persuasive evidence that placenta-derived extracellular vesicles (EVs) represent a significant intercellular communication pathway, and that they may play an important role in placental and endothelial cell (both fetal and maternal) function. These functions are known to be altered in PE. EVs can carry and transport a wide range of bioactive molescules that have potential to be used as biomarkers and therapeutic delivery tools for PE. EV content is often parent cell specific, thus providing an insight or "thumbprint" of the intracellular environment of the originating cell (e.g., human placenta). EV have been identified in plasma under both normal and pathological conditions, including PE. The concentration of EVs and their content in plasma has been reported to increase in association with disease severity and/or progression. Placenta-derived EVs have been identified in maternal plasma during normal pregnancy and PE pregnancies. They contain placenta-specific proteins and miRNAs and, as such, may be differentiated from maternally-derived EVs. The aim of this review, thus, is to describe the potential roles of EVs in preecmpatic pregnancies, focussing on EVs secreted from placental cells. The biogenesis, specificity of placental EVs, and methods used to characterise EVs in the context of PE pregnancies will be also discussed.

Objectives: Methamphetamine intoxication is an increasing cause of emergency department (ED) visits in the United States, particularly in the west. In San Francisco, California, 47% of patients visiting psychiatric emergency services are intoxicated with methamphetamine. Such patients often visit the ED due to acute psychiatric symptoms, yet ED-based research investigating the outcomes and resource utilization of these visits is limited., Methods: We examined a retrospective cohort of ED patients requiring ED-based psychiatric consultation from June 2017 to July 2018. We evaluated the association between methamphetamine visits and need for chemical restraint, psychiatric hospitalization, and length of stay (LOS)., Results: We identified 2,087 ED visits with psychiatric consults. Based on urine toxicology results and discharge diagnosis, 403 visits involved methamphetamine with or without other drugs, 480 involved other drugs without methamphetamine, and 1,204 had no evidence of drug use. Methamphetamine visits were associated with increased odds of chemical restraint compared to visits without drug use (adjusted odds ratio [AOR] = 3.2, 95% CI = 2.1 to 5.2, p < 0.001), but not other drug visits (AOR = 1.2, 95% CI = 0.8 to 1.9, p = 0.4). Methamphetamine visits had lower odds of psychiatric hospitalization than other drug visits (AOR = 0.62, 95% CI = 0.41 to 0.95, p = 0.03) and longer adjusted LOS than visits without drug use (+4.3 hours, 95% CI = 4.1 to 8.3 hours, p < 0.001) but not other drug visits (+1.5 hours, 95% CI = -0.6 to 3.7 hours, p = 0.2)., Conclusions: Methamphetamine ED visits were associated with increased odds of needing chemical restraint and of an increased ED LOS but not with psychiatric inpatient admission. These results indicate an opportunity to improve the efficiency of ED care for these patients., (© 2020 Society for Academic Emergency Medicine (SAEM).)

Spontaneous preterm birth is the leading cause of neonatal mortality and morbidity globally. Activation of the maternal immune system leads to a downstream cascade of proinflammatory events that culminate in the activation of spontaneous uterine contractions and the rupture of the foetal membranes. Anti-inflammatory agents may be a novel therapeutic approach to prevent inflammation-induced myometrial contractions and premature rupture of foetal membranes. The polyphenol gallic acid has been previously shown to exert potent anti-inflammatory effects. Thus, this study aimed to determine the effect of gallic acid on proinflammatory and pro-labour mediators in cytokine-stimulated gestational tissues in vitro. In primary human cells isolated from myometrium and foetal membranes (decidua, and amnion mesenchymal and epithelial cells), gallic acid treatment suppressed inflammation-induced expression of proinflammatory cytokines and chemokines and extracellular matrix-degrading and matrix-remodelling enzymes. Gallic acid also significantly inhibited inflammation-induced myometrial activation as evidenced by decreased expression of contraction-associated proteins, the uterotonic PGF2α and collagen cell contractility. Using a global proteomic approach, gallic acid may differentially regulate proteins associated with collagen synthesis, cell contractility and protein synthesis in primary myometrial and decidual cells. In summary, gallic acid inhibited inflammation-induced mediators involved in active labour in primary cells isolated from myometrium and foetal membranes. These in vitro studies suggest that the polyphenol gallic acid may be able to suppress the production of proinflammatory and pro-labour mediators involved in myometrial contractions and rupture of foetal membranes. Future preclinical studies may elucidate the efficacy of gallic acid in preventing inflammation-driven preterm birth.

Carboplatin, administered as a single drug or in combination with paclitaxel, is the standard chemotherapy treatment for patients with ovarian cancer (OVCA). Recent evidence suggests that miRNAs associated with small extracellular vesicles (sEVs) participate in the development of chemoresistance. We studied the effect of carboplatin in a heterogeneity population of OVCA cells and their derived sEVs to identify mechanisms associated with chemoresistance. sEVs were quantified using an engineered superparamagnetic material, gold-loaded ferric oxide nanotubes and a screen-printed electrode. miR-21-3p, miR-21-5p, and miR-891-5p are enriched in sEVs, and they contribute to carboplatin resistance in OVCA. Using a quantitative MS/MS, miR-21-5p activates glycolysis and increases the expression of ATP-binding cassette family and a detoxification enzyme. miR-21-3p and miR-891-5p increase the expression of proteins involved in DNA repair mechanisms. Interestingly, the levels of miR-891-5p within sEVs are significantly higher in patients at risk of ovarian cancer relapse. Identification of miRNAs in sEVs also provides the opportunity to track them in biological fluids to potentially determine patient response to chemotherapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The objective of this study was to quantify the differences in surface electromyogram (EMG) signal characteristics between affected and contralateral arm muscles of hemispheric stroke survivors. EMG signals were recorded from the biceps brachii muscles using single differential electrodes. Four chronic stroke subjects performed isometric elbow flexions at sub-maximal voluntary contraction levels on both the affected and contralateral limbs. The force generated on the contralateral side was matched to the force generated on the affected side. We observed different types of EMG activation on the affected side compared to the contralateral side.Specifically, two subjects showed lower RMS EMG activity on the affected side whereas two subjects showed greater EMG activity on the affected side compared to the contralateral side. Analysis of the peak amplitudes of the EMG activity showed greater number of peaks in the EMG on affected side compared to the contralateral side in all subjects. The histogram of the peak amplitudes showed greater number of smaller peak amplitudes in subjects with lower EMG activity on the affected side suggesting a reliance on smaller motor units. Our combined EMG signal analysis techniques on one set of recorded signals provides insight regarding potential mechanisms of weakness.Clinical Relevance- Decoding neural information from surface EMG signals without decomposition into individual motor units could provide clinicians with quick insight about disease progress and potential treatment.

Purpose: Neoadjuvant chemotherapy is a recommended treatment for patients with penile cancer with bulky inguinal lymphadenopathy or unresectable primary tumors, although there is no evidence of its benefit from randomized trials., Materials and Methods: We conducted a systematic search in Embase® and MEDLINE® for studies reporting on patients who received preoperative neoadjuvant chemotherapy for locally advanced penile squamous cell carcinoma. Objective response rate, pathological complete response, grade 3 or greater toxicity and overall mortality were evaluated in terms of neoadjuvant chemotherapy type, which was dichotomized as nontaxane-platinum and taxane-platinum regimens., Results: Overall 10 studies met the inclusion criteria, enrolling a total of 182 patients, with 66 (36.3%) and 116 (63.7%) treated with nontaxane-platinum and taxane-platinum regimens, respectively. The pooled results demonstrated an objective response rate of 53% (95% CI 42-64), pathological complete response rate of 16%, grade 3 or greater toxicity rate of 40% (95% CI 19-64) and overall mortality of 55% (95% CI 40-70) in patients treated with neoadjuvant chemotherapy. Stratified subanalysis revealed an objective response rate of 55% and 49%, a pathological complete response of 9% and 20%, a toxicity rate of 26% and 49%, and an overall mortality of 54% and 58% for nontaxane-platinum vs taxane-platinum regimens, respectively., Conclusions: The pooled findings in this study suggest that approximately 50% of the patients with bulky regional lymph node metastases from penile cancer respond to platinum based neoadjuvant chemotherapy and approximately 16% of patients achieve a pathological complete response. Nontaxane based regimens appear to be better tolerated than taxane regimens based on reported grade 3 or greater adverse events (26% vs 49%). Ultimately the robustness of these observations should be interpreted with an awareness of the inherent limitations of deriving data from a collection of small, heterogeneous series.

Background: Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is the most efficacious way to collect specimens from a solid lesion adjacent to the gastrointestinal tract and is performed with an internal stylet during puncture. However, its reinsertion into the needle is time-consuming. Controversy surrounds whether quality of cytology specimen improves with stylet use. We performed a meta-analysis comparing the use of stylet versus no stylet with EUS-FNA of gastrointestinal-related masses., Methods: Multiple databases were searched from inception until April 28, 2016. Discordant findings from independent extractions were reviewed by at least 2 investigators. Methods were executed as per the standards of the Cochrane Collaboration. Primary outcomes assessed were diagnostic adequacy of individual specimen samples, accuracy, and yield. Secondary outcomes included overall diagnostic accuracy of per-malignant lesion, cellularity, contamination, and bloodiness of the sample, and adverse events., Results: Five randomized control trials were identified comparing stylet versus no stylet use, which enrolled 504 patients, evaluated 537 lesions, and 1914 distinct specimens. There was no difference in diagnostic adequacy [risk ratio (RR)=1.00; 95% confidence interval (CI), 0.95-1.07], accuracy (RR=0.98; 95% CI, 0.90-1.06), or yield (RR=0.96; 95% CI, 0.89-1.03). No stylet use was favored in per-lesion malignant diagnosis (RR=0.85; 95% CI, 0.76-0.96). There was no difference in representative cellularity, contamination, or bloodiness of specimens obtained with or without stylet use., Conclusions: Stylet use confers no significant advantage in diagnostic adequacy, accuracy, yield, contamination, bloodiness, or cellularity over no stylet. We reinforce that no stylet use may be used preferentially in EUS-FNA as a more convenient technique and is favored with a higher per-lesion malignant diagnosis.

Introduction: More than 50% of patients with esophageal cancer already have inoperable disease at the time of diagnosis. Controversy surrounds the outcomes of patients with advanced esophageal cancer who receive palliative care by either stent alone or stent plus an additional modality. We set out to perform a systematic review and meta-analysis of studies assessing the use of metal stents as treatment options for symptomatic improvement, survival, and adverse events., Methods: We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception until January 14, 2016, as well as other databases for randomized controlled trials (RCTs) comparing esophageal stent versus either esophageal stent plus brachytherapy, radiotherapy, or chemotherapy. For quality assurance purposes throughout the systematic review, multiple independent extractions were performed, and the process was executed as per the standards of the Cochrane collaboration. Primary outcomes were mean change in dysphagia score, overall survival, and quality of life. Secondary outcomes were adverse events including fever, severe pain, aspiration, fistula, stent migration, perforation, and restenosis., Results: Eight RCTs enrolling 732 patients were included with three distinct comparisons: stents combination therapy vs stents alone (5 studies, n = 417), stents alone versus brachytherapy alone (2 studies, n = 274), and stents + brachytherapy vs brachytherapy alone (1 study, n = 41). Stents combination therapy was defined as stents plus radiotherapy, chemotherapy, or both. Mean change in dysphagia scores favored stents combination therapy versus stents alone, and the effect was seen in patients surviving longer than 3 months. Stents combination therapy was also associated with a more favorable overall survival. The risks of stent migration, aspiration pneumonia, and restenosis were lower in the stents combination group compared to stents alone, while the risks of severe pain, hemorrhage, and fistula formation were higher. Changes in dysphagia scores and overall survival did not differ significantly in the brachytherapy-alone vs stents-alone comparison. The risk of fistula formation and hemorrhage were higher in the stents-alone group, while the risk of perforation was lower, compared to brachytherapy alone. Quality of life improvements were seen in all treatment groups, but were not pooled in analysis due to differing methods of measurement., Discussion: While there appears to be no immediate short-term differences, those who live longer than 3 months experience a significant improvement in dysphagia score using a stents combination therapy approach vs stents alone. The combination therapy significantly improves the overall survival as well as showed improvements in quality of life scores. Larger randomized controlled trials are needed to assess improvements in dysphagia score, overall survival, quality of life, and adverse events.

Background: There is evidence that human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are independent risk factors for osteoporosis and fracture which is not solely explained by changes in bone mineral density. Thus, we hypothesized that the assessment of trabecular microstructure might play an important role for bone quality in this population and might explain the increased fracture risk. In this study, we have assessed bone microstructure in the proximal femur using high-resolution magnetic resonance imaging (MRI) as well as in the extremities using high resolution peripheral quantitative computed tomography (HR-pQCT) in HIV-infected men and healthy controls and compared these findings to those based on areal bone mineral density (aBMD) derived from dual X-ray absorptiometry (DXA) which is the standard clinical parameter for the diagnosis of osteoporosis., Methods: Eight HIV-infected men and 11 healthy age-matched controls were recruited and informed consent was obtained before each scan. High-resolution MRI of the proximal femur was performed using fully balanced steady state free precession (bSSFP) on a 3T system. Three volumes of interest at corresponding anatomic locations across all subjects were defined based on registrations of a common template. Four MR-based trabecular microstructural parameters were analyzed at each region: fuzzy bone volume fraction (f-BVF), trabecular number (Tb.N), thickness (Tb.Th), and spacing (Tb.Sp). In addition, the distal radius and distal tibia were imaged with HR-pQCT. Four HR-pQCT-based microstructural parameters were analyzed: trabecular bone volume fraction (BV/TV), Tb.N, Tb.Th, and Tb.Sp. Total hip and spine aBMD were determined from DXA., Results: Microstructural bone parameters derived from MRI at the proximal femur and from HR-pQCT at the distal tibia showed significantly lower bone quality in HIV-infected patients compared to healthy controls. In contrast, DXA aBMD data showed no significant differences between HIV-infected patients and healthy controls., Conclusions: Our results suggest that high-resolution imaging is a powerful tool to assess trabecular bone microstructure and can be used to assess bone health in HIV-infected men who show no differences to healthy males by DXA aBMD. Advances in MRI technology have made microstructural imaging at the proximal femur possible. Further studies in larger patient cohorts are clearly warranted., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Exosomes are membrane-bound nanovesicles that transport molecular signals (e.g., proteins) between cells and are released from a wide range of cells, including the human placenta. Interestingly, the levels of exosomes present in maternal circulation are higher in preeclamptic pregnancies and their protein content profile change in response to the microenvironment milieu. Through the discovery of candidate biomarkers, mass spectrometry (MS)-based proteomics may provide a better understanding of the pathophysiology underlying pregnancy-associated disorders. With advances in sample preparation techniques, computational methodologies, and bioinformatics, MS-based proteomics have addressed the challenge of identifying and quantifying thousands of proteins and peptides from a variety of complex biological samples. Despite increasing interest in biomarker diagnostics, the complex nature of biological matrices (e.g., plasma) poses a challenge for candidate biomarker discovery. Here we describe a workflow to prepare exosomes for proteomic analysis.

Exosomes are small (~100 nm) vesicles that carry a wide range of molecules including proteins, RNAs, and DNA. Exosomes are secreted from a wide range of cells including placental cells. Interestingly, exosomes secreted from placental cells have been identified in maternal circulation as early as in 6 weeks of gestation, and their concentration increases with the gestational age. While there is growing interest in elucidating the role of exosomes during normal and complicated pregnancies (such as preeclampsia), progress in the field has been delayed because of the inability to isolate placental exosomes from maternal circulation. Therefore, here we describe a workflow to isolate placental exosomes from maternal circulation.

Objectives: The aim of this study was to assess the feasibility of quantifying shoulder cartilage morphology and relaxometry in a clinically feasible scan time comparing different pulse sequences and assessing their reproducibility at 3 Tesla., Methods: Three pulse sequences were compared for morphological assessments of shoulder cartilage thickness and volume (SPGR, MERGE, FIESTA), while a combined T1ρ-T2 sequence was optimized for relaxometry measurements. The shoulders of six healthy subjects were scanned twice with repositioning, and the cartilage was segmented and quantified. The degree of agreement between the three morphological sequences was assessed using Bland-Altman plots, while the morphological and relaxometry reproducibility were assessed with root-mean-square coefficients of variation (RMS-CVs) RESULTS: Bland-Altman plots indicated good levels of agreement between the morphological assessments of the three sequences. The reproducibility of morphological assessments yielded RMS-CVs between 4.0 and 17.7 %. All sequences correlated highly (R > 0.9) for morphologic assessments with no statistically significant differences. For relaxometry assessments of humeral cartilage, RMS-CVs of 6.4 and 10.6 % were found for T1ρ and T2, respectively., Conclusions: The assessment of both cartilage morphology and relaxometry is feasible in the shoulder with SPGR, humeral head, and T1ρ being the more reproducible morphological sequence, anatomic region, and quantitative sequence, respectively., Key Points: • The thin cartilage morphology can be assessed in the shoulder in vivo. • Non-invasive biochemical assessment of shoulder cartilage is feasible in vivo using MRI.

Background: Compared with the Goutallier classification, chemical shift-based magnetic resonance (MR) fat quantification has superior reliability and accuracy in evaluation of muscle fatty infiltration. We used this method to assess the relationship between rotator cuff (RC) muscle fat fractions, tendon disease severity, and subject characteristics., Methods: In total, 182 subjects with shoulder symptoms underwent shoulder MR imaging including additional sequences for fat quantitation. Then, fat fraction maps were manually segmented, and custom software was used to compute the fat fraction. Goutallier scores were also obtained. The relationship between fat fraction and tendon tear severity and subject characteristics was assessed with descriptive statistics, analysis of variance, Student t test of different subgroups, and simple and multiple linear regression analysis., Results: Statistically higher supraspinatus fat fractions were observed in subgroups with tendon tears >3 cm, retraction >1 cm, age >50 years, body mass index (BMI) >30, higher Goutallier score, female gender, and longer symptom duration. A significant linear relationship was seen between RC fat fraction and tendon disease severity, age, and BMI but not symptom duration. Multiple regression models with fat fraction and tendon disease, age, BMI, and gender were significant for all 4 muscles (P < .001). The slope of fatty infiltration increase with age was reduced after adjustment for tendon disease, BMI, and gender., Conclusion: RC fat fraction assessed by chemical shift MR demonstrated a significant linear relationship with tendon tear severity, age, BMI, and gender but not with symptom duration., (Published by Elsevier Inc.)