Citations

Importance Urethral diverticulectomy is performed with or without concomitant pubovaginal sling (PVS). Patients with complex UD are more frequently offered concomitant PVS. However, there is paucity of literature comparing postoperative incontinence rates for patients with simple versus complex UD. Objective The objective of this study is to examine postoperative stress urinary incontinence (SUI) rates after Urethral Diverticulectomy without concomitant PVS for both complex and simple cases. Study Design A retrospective cohort study was conducted among 55 patients who underwent Urethral Diverticulectomy from 2007 to 2021. Preoperative SUI was patient-reported and confirmed with cough stress test result. Complex cases were defined as circumferential or horseshoe configurations, prior diverticulectomy, and/or anti-incontinence procedure. Primary outcome was postoperative SUI. Secondary outcome was interval PVS. Complex and simple cases were compared using the Fisher exact test. Results Median age was 49 years (interquartile range, 36–58 years). Median follow-up was 5.4 months (IQR, 2–24 months). Thirty of 55 (55%) cases were simple, and 25 of 55 (45%) complex. Preoperative SUI was present in 19/57 (35%) (11 complex vs 8 simple, P = 0.25). Stress urinary incontinence persisted postoperatively in 10 of 19 (52%) (6 complex vs 4 simple, P = 0.48). De novo SUI occurred in 7 of 55, 12% (4 complex vs 3 simple, P = 0.68). Overall, 17 of 55 (31%) patients had postoperative SUI (10 complex vs 7 simple, P = 0.24). Of those, 8 of 17 underwent subsequent PVS placement (P = 0.71) and 9 of 17 had resolution of pad use after physical therapy (P = 0.27). Conclusions We did not find evidence of an association between complexity and postoperative SUI. Age at surgery and preoperative frequency were the strongest predictors of postoperative SUI in this cohort. Our findings suggest successful complex urethral diverticulum repair does not require concomitant PVS.

Abstract Outpatient parenteral antimicrobial therapy (OPAT) has become more common in clinical settings. Correspondingly, OPAT-related publications have also increased; the objective of this article was to summarize clinically meaningful OPAT-related publications in 2022. Seventy-five articles were initially identified, with 54 being scored. The top 20 OPAT articles published in 2022 were reviewed by a group of multidisciplinary OPAT clinicians. This article provides a summary of the “top 10” OPAT publications of 2022.

Importance Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown. Objective To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported nonvigorous activity. Design, Setting, and Participants This was an investigator-initiated, prospective cohort study. Participants were enrolled from May 18, 2015, to April 25, 2019, with completion in February 28, 2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous-intensity exercise. This was a multicenter, observational registry with recruitment at 42 high-volume HCM centers in the US and internationally; patients could also self-enroll through the central site. Individuals aged 8 to 60 years diagnosed with HCM or genotype positive without left ventricular hypertrophy (phenotype negative) without conditions precluding exercise were enrolled. Exposures Amount and intensity of physical activity. Main Outcomes and Measures The primary prespecified composite end point included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate shock from an implantable cardioverter defibrillator. All outcome events were adjudicated by an events committee blinded to the patient’s exercise category. Results Among the 1660 total participants (mean [SD] age, 39 [15] years; 996 male [60%]), 252 (15%) were classified as sedentary, and 709 (43%) participated in moderate exercise. Among the 699 individuals (42%) who participated in vigorous-intensity exercise, 259 (37%) participated competitively. A total of 77 individuals (4.6%) reached the composite end point. These individuals included 44 (4.6%) of those classified as nonvigorous and 33 (4.7%) of those classified as vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years, respectively. In multivariate Cox regression analysis of the primary composite end point, individuals engaging in vigorous exercise did not experience a higher rate of events compared with the nonvigorous group with an adjusted hazard ratio of 1.01. The upper 95% 1-sided confidence level was 1.48, which was below the prespecified boundary of 1.5 for noninferiority. Conclusions and Relevance Results of this cohort study suggest that among individuals with HCM or those who are genotype positive/phenotype negative and are treated in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or those who were sedentary. These data may inform discussion between the patient and their expert clinician around exercise participation.

Summary: Fewer than half of all patients undergoing surgery report adequate postoperative pain relief. Poorly managed postoperative pain can lead to complications, increased hospital stays, prolonged rehabilitation, and a decreased quality of life. Pain rating scales are commonly used to identify, manage, and track the perceived intensity of pain. Changes in perceived pain severity and intensity are a key indicator for course of treatment. Postoperative pain is best treated with multimodal management with a variety of analgesic medications and techniques that target different receptors and mechanisms of action in the peripheral and central nervous systems. This includes systemic analgesia, regional analgesia, local analgesia (eg, topical and tumescent analgesia), and nonpharmacologic modalities. It is recommended that this approach is individually tailored and discussed through a shared decision-making approach. This review provides an overview of multimodal management for acute postoperative pain related to plastic surgery procedures. To increase patient satisfaction and provide effective pain control, it is recommended to educate patients on expectations of pain, multimodal options for pain control (including peripheral nerve blocks), complications of unrelieved pain, tracking and monitoring of pain by self-reporting, and how to reduce the use of opioid-based pain medication.

Background: There is a significant long-term risk of posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament reconstruction (ACLR). Elucidating the risk factors and successfully identifying at-risk patients is challenging. Purpose/Hypothesis: The purpose of this study was to produce machine learning survival models that can identify (1) patients at risk of symptomatic PTOA and (2) patients who are at risk of undergoing total knee arthroplasty (TKA) after ACLR. It was hypothesized that these models would outperform traditional Kaplan-Meier estimators. Study Design: Case-control study; Level of evidence, 3. Methods: A geographic database was used to identify patients undergoing ACLR between 1990 and 2016 with a minimum 7.5-year follow-up. Models were used to analyze various factors to predict the rate and time to (1) symptomatic osteoarthritis and (2) TKA using random survival forest (RSF) algorithms. Performance was measured using out-of-bag (OOB) c-statistic, calibration, and Brier score. The predictive performances of the RSF models were compared with Kaplan-Meier estimators. Model interpretability was enhanced utilizing global variable importance and partial dependence curves. Results: A total of 974 patients with ACLR and a minimum follow-up of 7.5 years were included; among these, 215 (22.1%) developed symptomatic osteoarthritis, and 25 (2.6%) progressed to TKA. The RSF algorithms achieved acceptable good to excellent predictive performance for symptomatic arthritis (OOB c-statistic, 0.75; Brier score, 0.128) and progression to TKA (OOB c-statistic, 0.89; Brier score, 0.026), respectively. Significant predictors of symptomatic PTOA included increased pain scores, older age, increased body mass index, increased time to ACLR, total number of arthroscopic surgeries before the diagnosis of arthritis, positive pivot-shift test after reconstruction, concomitant chondral injury, secondary meniscal tear, early (<250 days) or delayed (>500 days) return to sports or activity, and use of allograft. Significant predictors for TKA included older age, increased pain scores, total number of arthroscopic surgeries, high-demand activity/occupation, hypermobility, higher body mass index, systemic inflammatory disease, increased time to surgery, early (<250 days) or delayed (>500 days) return to sports or activity, and midsubstance tears. The Brier score over time revealed that RSF models outperformed traditional Kaplan-Meier estimators. Conclusion: Machine learning survival models were used to reliably identify patients at risk of developing symptomatic PTOA, and these models consistently outperformed traditional Kaplan-Meier estimators. Strong predictors for the development of PTOA after ACLR included increased pain scores at injury and postoperative visit, older age at injury, total number of arthroscopic procedures, positive postoperative pivot-shift test, and secondary meniscal tear.

Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. Therefore, methods to comprehensively analyze all glyco-polymer classes on EVs are urgently needed. In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. The results indicate that GNA can identify EV-associated glyco-polymers that would remain undetected with conventional MS methods. Specifically, predictions based on GNA identified a GAG (hyaluronan) with varying abundance on EVs from two different melanoma cell lines. Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. These results lay the framework to explore GNA as a tool to assess major glycan classes on EVs, unveiling the EV glycocode and its biological functions.

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3−, MCP-2−, and IL20-dependent pathways.

These NCCN Guidelines for Distress Management discuss the identification and treatment of psychosocial problems in patients with cancer. All patients experience some level of distress associated with a cancer diagnosis and the effects of the disease and its treatment regardless of the stage of disease. Clinically significant levels of distress occur in a subset of patients, and identification and treatment of distress are of utmost importance. The NCCN Distress Management Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights describe updates to the NCCN Distress Thermometer (DT) and Problem List, and to the treatment algorithms for patients with trauma- and stressor-related disorders.