ACR Appropriateness Criteria® Workup of Pleural Effusion or Pleural Disease.

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.

Chemically-Induced Lipoprotein Breakdown for Improved Extracellular Vesicle Purification.

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.

Intensive Versus Traditional Cardiac Rehabilitation: Mortality and Cardiovascular Outcomes in a 2016-2020 Retrospective Medicare Cohort.

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.

Surgical treatment of benign prostatic hyperplasia: Thulium enucleation versus single-port transvesical robotic simple prostatectomy.

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.

Retrograde incision from orifice (RIO) technique for endoscopic incision of ureterocele: 15 years of outcomes.

INTRODUCTION: Management of obstructing ureterocele often includes endoscopic transurethral incision (TUI) that can be challenging secondary to uncertainty in anatomic landmarks with risk of serious complications. To this end, we innovated a technique using predictable landmarks that begins endoscopic incision at the ureterocele orifice and extends retrograde proximal to the bladder neck (Figure). OBJECTIVE: With over 15 years of experience in performing this retrograde incision from orifice (RIO) technique, we aimed to examine post-operative outcomes and risk of surgical failure after RIO compared to traditional TUI techniques for ureteroceles. We hypothesized that clinical outcomes after RIO would be superior to traditional endoscopic approaches to decompression of obstructing ureterocele in infants. STUDY DESIGN: A retrospective study of patients ≤12 months old who underwent TUI ureterocele at our institution between 2007 and -2021 was conducted. Pre-, intra- and post-operative characteristics were compared between patients who underwent RIO vs non-RIO TUI. Primary outcome was post-incision febrile urinary tract infection (fUTI). Secondary outcome was a composite failure measure of fUTI, secondary surgery, de novo bladder outlet obstruction, or vesicoureteral reflux. Multivariable Cox proportional hazard models were fitted to compare the time-to-event risk of primary and secondary outcomes between groups. RESULTS: Ninety patients with 92 ureteroceles were included (49 RIO, 43 non-RIO). Median follow-up from TUI was 33 months. RIO had a shorter median operative duration (27 vs 35 min, p = 0.021). Primary and secondary outcomes were similar between groups (fUTI: 29% RIO vs 19% non-RIO, p = 0.27; composite failure 54% RIO vs 69% non-RIO, p = 0.15). In multivariable Cox proportional hazard models, there was no significant difference in risk of fUTI (RIO aHR 0.98, 95% CI 0.38-2.54, p = 0.97) or composite failure (RIO aHR 0.80, 95% CI 0.45-1.44, p = 0.46) between TUI techniques. DISCUSSION: RIO technique for TUI ureterocele is attractive in that it uses predictable anatomic landmarks making it simple to perform. In analyzing this 15-year institutional experience of TUI ureterocele, RIO showed similar success to non-RIO endoscopic incisions. This study is a retrospective, non-randomized, single-institutional study over 15 years and is therefore subject to change in surgeon practice over time and variable practices between providers. CONCLUSIONS: Given comparable success and durability over time to other TUI ureterocele techniques, and with the advantage of operator ease using consistent anatomic landmarks, RIO is a worthy option for endoscopic ureterocele decompression.

Extracellular vesicles as mediators of cell-cell communication in ovarian cancer and beyond - A lipids focus.

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.

Robot-assisted Laparoscopic Pyeloplasty: Experience of a Single Pediatric Institution, Including Long-term and Safety Outcomes.

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.

The impact of obesity and uncontrolled asthma during pregnancy on metabolic and inflammatory pathways.

OBJECTIVE: Asthma and obesity are both inflammatory complications of pregnancy and when combined contribute to an increased risk of uncontrolled asthma during pregnancy and poor perinatal outcomes. Our previous work has identified the presence of maternal asthma is associated with a proinflammatory milieu in the placenta and reduced fetal growth. The current study was designed to determine the relationships between immunomodulatory metabolic pathways and inflammation and establish whether these pathways are associated with uncontrolled asthma in obese pregnant women. METHODS: Fifty-three obese (BMI >30) pregnant women were recruited prospectively. Participants were classified as having no asthma, controlled asthma, and uncontrolled asthma based on a doctor diagnosis and assessment using the Asthma Control Questionnaire (ACQ). Circulating plasma concentrations of metabolic hormones leptin, adiponectin, insulin, glucose, and extracellular vesicle (EVs) associated cytokines were measured at 18- and 36-weeks gestation. RESULTS: Concentrations of metabolic and inflammatory markers among obese participants with or without asthma were not significantly different throughout gestation. However total adiponectin concentrations increased as gestation progressed in obese, non-asthmatic women but did not increase in women with asthma. Plasma adiponectin and leptin levels in women with uncontrolled asthma were positively correlated with EV inflammatory markers including GM-CSF, IL-6, TNFα and IFNγ protein. CONCLUSIONS: This study demonstrated that most metabolic markers remain unchanged with the presence and severity of asthma in obese pregnant women. However, differences in the associations between metabolic and inflammatory pathways were observed in women with asthma and may be one of the mechanisms contributing to uncontrolled asthma in obese pregnant women.

Gender-affirming vaginoplasty: Technical considerations in patients with genital skin deficiency.

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.

World professional association for transgender health guidelines: 2022 surgical treatment updates in the standards of care for transgender and gender diverse people.

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.

Peptide-based LDH5 inhibitors enter cancer cells and impair proliferation.

Lactate dehydrogenase 5 (LDH5) is overexpressed in many cancers and is a potential target for anticancer therapy due to its role in aerobic glycolysis. Small-molecule drugs have been developed as competitive inhibitors to bind substrate/cofactor sites of LDH5, but none reached the clinic to date. Recently, we designed the first LDH5 non-competitive inhibitor, cGmC9, a peptide that inhibits protein-protein interactions required for LDH5 enzymatic activity. Peptides are gaining a large interest as anticancer agents to modulate intracellular protein-protein interactions not targetable by small molecules; however, delivery of these peptides to the cytosol, where LDH5 and other anticancer targets are located, remains a challenge for this class of therapeutics. In this study, we focused on the cellular internalisation of cGmC9 to achieve LDH5 inhibition in the cytosol. We designed cGmC9 analogues and compared them for LDH5 inhibition, cellular uptake, toxicity, and antiproliferation against a panel of cancer cell lines. The lead analogue, [R/r]cGmC9, specifically impairs proliferation of cancer cell lines with high glycolytic profiles. Proteomics analysis showed expected metabolic changes in response to decreased glycolysis. This is the first report of a peptide-based LDH5 inhibitor able to modulate cancer metabolism and kill cancer cells that are glycolytic. The current study demonstrates the potential of using peptides as inhibitors of intracellular protein-protein interactions relevant for cancer pathways and shows that active peptides can be rationally designed to improve their cell permeation.

ACR Appropriateness Criteria® Staging and Follow-Up of Esophageal Cancer.

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.

ACR Appropriateness Criteria® Suspected Pulmonary Hypertension: 2022 Update.

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.

A novel technique using chronic infusion of small extracellular vesicles from gestational diabetes mellitus causes glucose intolerance in pregnant mice.

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.

Single-Port Robotic Surgery: General Principles and Troubleshooting.

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.

Targeted Mass Spectrometry-Based Proteomics Method to Quantify Placental Extracellular Vesicles.

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.