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Abstract: Extracorporeal membrane oxygenation (ECMO) is a type of mechanical circulatory support that is increasingly utilized in the United States for severe respiratory and/or cardiac failure refractory to conventional therapies. It is an expensive and complex life support modality. Moreover, patients on ECMO are critically ill and require a strong multidisciplinary care team. A successful ECMO program involves a trained team consisting of physicians, perfusionists, nurses, and respiratory therapists. This article discusses the multiple roles of ECMO nurses, the various ECMO delivery care models, and the potential cost savings of an RN ECMO specialist staffing model-and introduces the novel role of the ECMO lead., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The ureteral access sheath (UAS) is a medical device that enables repeated entrance into the ureter and collecting system during retrograde intrarenal surgery (RIRS). Its impact on stone-free rates, ureteral injuries, operative time, and postoperative complications remains controversial. Therefore, we performed a systematic review and meta-analysis comparing RIRS with versus without UAS for urolithiasis management., Purpose: To compare outcomes from retrograde intrarenal surgery (RIRS) for stone extraction with or without ureteral access sheath (UAS); evaluating stone-free rate (SFR), ureteral injuries, operative time, and postoperative complications., Materials and Methods: We systematically searched PubMed, Embase, and Cochrane Library in June 2024 for randomized controlled trials (RCTs) evaluating the efficacy and safety outcomes of UAS use in RIRS for urolithiasis treatment. Articles published between 2014 and 2024 were included. Pooled risk ratios (RRs) and mean differences (MDs) were calculated for binary and continuous outcomes, respectively., Results: Five RCTs comprising 466 procedures were included. Of these, 246 (52.7%) utilized UAS. The follow-up ranged from 1 week to 1 month. UAS reduced the incidence of postoperative fever (RR 0.49; 95% confidence interval [CI] 0.29-0.84; p=0.009), and postoperative infection (RR 0.50; 95% CI 0.30-0.83; p=0.008). There were no significant differences between groups in terms of SFR (RR 1.05; 95% CI 0.99-1.11; p=0.10), ureteral injuries (RR 1.29; 95% CI 0.95-1.75; p=0.11), operative time (MD 3.56 minutes; 95% CI -4.15 to 11.27 minutes; p=0.36), or length of stay (MD 0.32 days; 95% CI -0.42 to 1.07 days; p=0.40)., Conclusion: UAS leads to a lower rate of post-operative fever and infection. However, UAS did not significantly reduce or increase the SFR or the rate of ureteral injuries during RIRS for patients with urolithiasis. The use of UAS should be considered to decrease the risk of infectious complications, particularly in those who may be at higher risk for such complications., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Introduction: Gender-affirming genital surgery is one of several surgical procedures available to transgender and nonbinary (TGNB) individuals to improve congruence between their gender identity and sex assigned at birth. Despite increasing utilization of these procedures, patient-reported outcome measures (PROMs) to assess subjective outcomes following gender-affirming genital surgery remain limited. Our aim was to provide a synopsis of PROMs currently being used to evaluate urinary outcomes among TGNB patients following gender-affirming genital surgery and to assess each PROM for content that is relevant to TGNB patients., Methods: A multidatabase search was performed (Embase and PubMed) using search terms that included transgender, patient-reported outcome measures, questionnaire, and gender-affirming surgery. Studies that assessed subjective outcomes related to urinary outcomes and pelvic floor dysfunction following gender-affirming genital surgery were reviewed. Gender-affirming genital surgery included vaginal reconstruction (vaginoplasty) and penile reconstruction (phalloplasty and metoidioplasty). Included studies were evaluated for relevant content items and summarized in table., Results: Our literature search identified 820 unique articles. Twenty-seven full articles were included in the final review. Until recently, measurement tools have been limited to unvalidated ad hoc questionnaires or PROMs developed for other conditions, such as urinary incontinence or vaginal prolapse, that are validated among the predominantly cisgender general population. Of the selected studies, PROMs used to evaluate urinary and pelvic floor dysfunction following gender-affirming genital surgery included self-construced ad hoc questionnaires (10 studies), Amsterdam Overactive Pelvic Floor Scale (four studies), King's Health Questionnaire (two studies), Pelvic Floor Distress Inventory (PFDI)-20 (two studies), Sheffield Pelvic Organ Prolapse (one study), International Consultation on Incontinence Questionnaire-Urinary Incontinence (ICIQ-UI) (one study), and ICIQ-Female Lower Urinary Tract Symptoms (one study). The PFDI-20 asked about the most relevant symptoms to TGNB patients following genital surgery; however, not all cisgender validated questionnaires included important questions about voiding position, splayed or misdirected stream. The Affirming Surgery Form and Function Individual Reporting Measure (AFFIRM) questionnaire is the first PROM for assessing subjective urinary outcomes that are validated for TGNB individuals, and the GENDER-Q is a promising new PROM with the aim of evaluating outcomes following surgical and other gender-affirming treatments., Conclusion: Despite recent advancements, a need remains for standardized assessment tools to evaluate pelvic floor dysfunction and urinary symptoms following gender-affirming genital surgery. Questionnaires developed for the general population to assess symptoms of pelvic organ prolapse and other urinary dysfunction do not fully capture the experiences unique to TGNB individuals undergoing this type of surgery. Nonetheless, PROMs validated specifically for TGNB individuals are necessary to more accurately evaluate outcomes of gender-affirming genital surgery, allow for informed patient counseling, and create evidence-based changes to improve these interventions., (© 2024 Wiley Periodicals LLC.)

Background: Retained hemothorax (rHTX) requiring intervention occurs in up to 20% of patients who undergo chest tube (TT) placement for a hemothorax (HTX). Thoracic irrigation at the time of TT placement decreases the need for secondary intervention in this patient group but those findings are limited because of the single-center design. A multicenter study was conducted to evaluate the effectiveness of thoracic irrigation., Methods: A multicenter, prospective, observational study was conducted between June 2018 and July 2023. Eleven sites contributed patients. Patients were included if they had a TT placed for a HTX and were excluded if: younger than 18 years, TT for pneumothorax, thoracotomy or video-assisted thoracoscopic surgery performed within 6 hours of TT, TT >24 hours after injury, TT removed <24 hours, or death within 48 hours. Thoracic irrigation was performed at the discretion of the attending. Each hemithorax was considered separately if bilateral HTX. The primary outcome was secondary intervention for HTX-related complications (rHTX, effusion, or empyema). Secondary intervention was defined as: TT placement, instillation of thrombolytics, video-assisted thoracoscopic surgery, or thoracotomy. Irrigated and nonirrigated hemithoraces were compared using a propensity weighted analysis with age, sex, mechanism of injury, Abbreviated Injury Scale chest, and TT size as predictors., Results: Four hundred ninety-three patients with 462 treated hemothoraces were included, 123 (25%) had thoracic irrigation at TT placement. There were no significant demographic differences between the cohorts. Fifty-seven secondary interventions were performed, 10 (8%) and 47 (13%) in the irrigated and non-irrigated groups, respectively ( p = 0.015). Propensity weighted analysis demonstrated a reduction in secondary interventions in the irrigated cohort (odds ratio, 0.56 (0.34-0.85); p = 0.005)., Conclusion: This Western Trauma Association multicenter study demonstrates a benefit of thoracic irrigation at the time of TT placement for a HTX. Thoracic irrigation reduces the odds of a secondary intervention for rHTX-related complications by 44%., Level of Evidence: Therapeutic/Care Management; Level II., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This paper proposes a smartphone-based method for measuring Blood Pressure (BP) using the oscillometric method. For oscillometry, it is necessary to measure (1) the pressure applied to the artery and (2) the local blood volume change. This is accomplished by performing an oscillometric measurement at the finger's digital artery, whereby a user presses down on the phone's camera with steadily increasing force. The camera is used to capture the blood volume change using photoplethysmography. We devised a novel method for measuring the force applied of the finger without the use of specialized smartphone hardware with a technique called Vibrometric Force Estimation (VFE). The fundamental concept of VFE relies on a phenomenon where a vibrating object is dampened when an external force is applied on to it. This phenomenon can be recreated using the phone's own vibration motor and measured using the phone's Inertial Measurement Unit (IMU). A cross device reliability study with three smartphones of different manufacturers, shape, and prices results in similar force estimation performance across all smartphone models. In an N = 24 proof of concept study of the BP measurement, the smartphone technique achieves a mean absolute error of 9.21 mmHg and 7.77 mmHg of systolic and diastolic BP, respectively, compared to an FDA approved BP cuff. The vision for this technology is not necessarily to replace existing BP monitoring solutions, but rather to introduce a downloadable smartphone software application that could serve as a low-barrier hypertension screening measurement fit for widespread adoption., (© 2024. The Author(s).)

Purpose: The availability of targeted therapies for advanced prostate cancer led to the expansion of national guidelines recommending germline genetic testing. The aim of this study was to describe recent trends in germline test ordering patterns for patients with prostate cancer., Materials and Methods: A retrospective cohort analysis of patients with prostate cancer who underwent germline testing through a single commercial laboratory (Invitae Corporation) between 2015-2020 was performed. Ordering trends between provider medical specialties were compared. Our primary hypothesis was that the proportion of tests ordered by urologists would increase over time., Results: In total, 17,256 prostate cancer patients underwent germline genetic testing; 14,400 patients had an ordering provider with an associated medical specialty and were included in the final comparison cohort. Total prostate cancer patients undergoing germline testing increased quarterly from 21 in Q2 of 2015 to 1,509 in Q3 of 2020. The proportion of tests ordered by urologists increased from 0% in Q2 2015 to 8.3% in Q3 2020 (P < 0.001). Compared to medical genetics, medical oncology, and other specialties, urology ordered more tests for patients under 70 years old (66% vs 51%-55%, P <0.004) and for patients who reported negative family history (25% vs 12%-20%, P = 0.012)., Conclusions: As awareness and indications for germline testing continue to expand, aggregate ordering volume is increasing, and urologists are becoming more involved in facilitating testing. This highlights the continued importance of educating urologists on the indications for and implications of germline genetic testing, as well as providing tools to support implementation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sarah Nielsen reports a relationship with Invitae Corporation that includes: employment. If there are other authors, they 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 © 2024 Elsevier Inc. All rights reserved.)

Metformin administration has recently emerged as a candidate strategy for the prevention of head and neck squamous cell carcinoma (HNSCC). However, the intricate relationship between genetic alterations in HNSCC and metformin sensitivity is still poorly understood, which prevents the stratifications of patients harboring oral premalignant lesions that may benefit from the chemopreventive activity of metformin. In this study, we investigate the impact of prevalent mutations in HNSCC in response to metformin. Notably, we found that the expression of oncogenic HRAS mutants confers resistance to metformin in isogenic HNSCC cell systems and that HNSCC cells harboring endogenous HRAS mutations display limited sensitivity to metformin. Remarkably, we found that metformin fails to reduce activation of the mTOR pathway in HRAS oncogene expressing HNSCC cells in vitro and in vivo, correlating with reduced tumor suppressive activity. Mechanistically, we found that this process depends on the ability of HRAS to enhance glycolytic metabolism, thereby suppressing the requirement of oxidative phosphorylation to maintain the cellular energetic balance. Overall, our study revealed that HNSCC cells with oncogenic HRAS mutations exhibit diminished metformin sensitivity, thus shedding light on a potential mechanism of treatment resistance. This finding may also help explain the limited clinical responses to metformin in cancers with RAS mutations. Ultimately, our study underscores the importance of understanding the impact of the genetic landscape in tailoring precision cancer preventive approaches in the context of HNSCC and other cancers that are characterized by the presence of a defined premalignant state and, therefore, amenable for cancer interception strategies.

Rattlesnake envenomations account for many of the Crotalid envenomations in the United States annually. Two antivenoms are currently available to treat Crotalid envenomation in this country: Crotalidae-polyvalent ovine immune Fab antivenom (CroFab®; FabAV) and Crotalidae equine immune F(ab')₂ antivenom (ANAVIP®; F(ab')₂AV). Few studies have compared the adverse effect rates for each. We performed a retrospective chart review of rattlesnake envenomations called to the California Poison Control System from October 2018 to August 2022. Those treated at healthcare facilities with either antivenom were included. Those treated with both antivenoms were excluded. Records were obtained from the poison center electronic medical records system. Demographic and clinical data were abstracted. "Severe" adverse events were defined as multi-organ system involvement, swelling of the patient's airway, and/or hemodynamic instability. All others were categorized as "non-severe." A total of 481 cases were included with 360 treated with FabAV and 121 with F(ab')₂AV. The median age was 47 and 46 years, and 72 % and 73 % were male, respectively. Clinical signs and symptoms of envenomation were similar in each group. The FabAV group received a median of six vials. The F(ab')₂AV group received a median of 10 vials, based on the recommended loading doses of FabAV and F(ab') 2 AV. Following antivenom administration, 18 individual acute non-severe AEs were reported in 12 FabAV-treated patients. Two acute non-severe AEs were reported in two F(ab')₂AV-treated patients. Rash or urticaria was the most commonly reported adverse effect in both groups after antivenom administration. Five patients (1.5 %) had severe adverse events reported in the poison center records following FabAV administration, and none were reported following F(ab')₂AV administration (p = 0.025). Overall, our poison center data suggests the rate of adverse events is low following the use of either antivenom. Our findings are limited by the lack of consistent timing data, a smaller F(ab')₂AV cohort, retrospective format, and use of poison center data., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Infection following tissue expander (TE) breast reconstruction is frequent and impactful. Preliminary reports demonstrate value of local antibiotic delivery for implant salvage and prophylactic potential. Herein is a multi-institutional retrospective study employing surgeon-crafted tobramycin-vancomycin PMMA plates (PLATE) during TE implantation for infection prophylaxis. The authors hypothesized the intervention would be associated with fewer infections compared to historical practice., Methods: In 2021, surgeons at three institutions began independently offering PLATE for primary TE breast reconstructions. After independent IRB approvals, data were retrospectively collected for PLATE subjects and pre-intervention cohorts of equivalent sizes. Subjects were followed for seven months, or to second stage removal. The primary outcome, complication requiring readmission/reoperation, was compared between aggregated cohorts. Analysis included logistic modeling and Kaplan-Meyer survival., Results: The aggregate sample included 183 intervention subjects (292 breasts) and 183 controls (301 breasts), each with 5+/-2-month follow-up. Overall, complications were significantly less frequent with PLATE (13.1% vs 21.9%, p<0.01*). This was driven by significantly fewer infections (4.8% vs 12.6%, p<0.01*) with no difference in rates of tissue necrosis, seroma, or other complications (p>0.05). In multivariable regression, the intervention was associated with significantly reduced odds of any complication (OR=0.53, 95%CI: [0.3-0.93]) and infection (OR=0.22, 95%CI: [0.08-0.50]). Kaplan-Meyer curves demonstrated significant longitudinal reduction in complication and infection (p<0.01*) without notable rebound throughout dissipation of the antibiotic eluent., Conclusion: Prophylactic employment of intraoperatively-crafted PLATE during TE implantation was associated with significant infection reduction without increase in local or systemic complications. This reproducible tool may be highly valuable in alloplastic breast reconstruction., Competing Interests: Financial Disclosure Statement: None of the authors disclose conflict of interest related to this work. No funding or assistance was received for this work., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Background: The role of dual checkpoint inhibition in advanced rare/ultra-rare non-epithelial ovarian cancers (NEOCs) is yet to be explored., Methods: DART is a prospective, multicenter (1,016 US sites), multi-cohort, single-arm phase II trial conducted through the Early Therapeutics and Rare Cancer SWOG/NCI Committee, assessing ipilimumab (anti-CTLA-4) (1mg/kg every 6 weeks) and nivolumab (anti-PD-1) (240mg every 2 weeks) in adults with advanced NEOCs who lack beneficial standard therapy. Primary outcome was overall response rate [ORR; complete response (CR)/partial response (PR)]; secondary outcomes were progression-free survival (PFS), overall survival (OS), clinical benefit rate [CBR; stable disease (SD) ≥6 months plus ORR], and toxicity., Results: Seventeen patients (median age: 64; number of prior therapies ranged from 0-8 with no immunotherapy exposure; 8 granulosa, 6 carcinosarcomas, 1 Sertoli-Leydig, 1 yolk sac, 1 Wolffian) were evaluated. In granulosa cell tumors, ORR was 25% (n=2/8; 1 CR, 1 PR) and CBR, 50% (n=4/8); PFS of 58.3 (CR), 50.7+ (PR), 30.4 (SD), and 8.7 (SD) months. Median PFS was 3.5 months (95% confidence intervals (CI) 1.7-11.2 months); median OS, 42.5 months (95% CI 10.1 months-not reached). One Sertoli-Leydig cell tumor showed a 22% regression (PFS 11.2 months). Carcinosarcomas had no response. Three participants (18%) discontinued treatment due to grade 3-4 adverse events., Conclusions: Ipilimumab-nivolumab shows activity in treatment-refractory granulosa cell tumors, with 25% (n=2/8) of patients experiencing either CR or PR lasting over 4 years.​.

Objective: We sought to develop a preoperative nomogram called NODESAFE (NODE SAFEty) to predict nodal involvement (NI) at time of surgery or subsequent follow up in localized renal cell carcinoma (RCC), as the role of lymphadenectomy in localized RCC remains controversial., Methods: We conducted a multicenter retrospective analysis of RCC patients who underwent primary surgical resection. Patients with clinical metastasis at presentation were excluded. NI was defined as presence of histological RCC with lymphadenectomy at time of surgery, or subsequent development histologically proven NI. The dataset was divided into training (70%) and testing subsets to facilitate model evaluation which was constructed through a stepwise multivariable logistic regression (MLR) model. Accuracy was tested with receiver operator characteristic estimated area under the curve (AUC)., Results: Total 3308 patients (2221 [67.1%] male) met inclusion criteria. During follow-up 25 patients (0.76 %) experienced nodal recurrence, and 22/25 were preoperatively classified as cN0. In our cohort, 112 (3.4%) patients had clinical lymphadenopathy preoperatively (cN1), and 34/112 were pN1. The following covariates were found to be statically significant on a MLR model: hypertension (Odds ratio [OR] 3.35, < .001), Charlson Comorbidity Index ≥ 5 (OR 1.93 P = .025), tumor size ≥ 6 cm (OR 2.63, P = .001), tumor necrosis at CT scan (OR 1.83, P = .036), cN1 (OR 5.59, P < .001) and CRP ≥ 8.5 mg/L (1.96, P = .018). Testing the prediction performance of the model in the validation set AUC of the model was 0.89. NODESAFE demonstrated a sensitivity of 83.9%, specificity of 86.1% and 99.1% negative predictive values using a 4% threshold probability., Conclusion: Combining clinical features, serum biomarkers and radiographic findings, we developed a model capable of predicting NI with high degree of accuracy. NODESAFE may refine clinical decision making with respect to the performance of lymphadenectomy at the time of surgery, postsurgical surveillance, and spur consideration for adjuvant therapy., Competing Interests: Disclosure No authors have any conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The purpose of the present study is to develop a calibration method to account for differences in echo times (TE) and facilitate the use of restriction spectrum imaging restriction score (RSIrs) as a quantitative biomarker for the detection of clinically significant prostate cancer (csPCa)., Methods: This study included 197 consecutive patients who underwent MRI and biopsy examination; 97 were diagnosed with csPCa (grade group ≥ 2). RSI data were acquired three times during the same session: twice at minimum TE ~75 ms and once at TE = 90 ms (TEmin 1 , TEmin 2 , and TE90, respectively). A linear regression model was determined to match the C-maps of TE90 to the reference C-maps of TEmin 1 within the interval ranging from 95th to 99th percentile of signal intensity within the prostate. RSIrs comparisons were made at the 98th percentile within each patient's prostate. We compared RSIrs from calibrated TE90 (RSIrs TE90corr ) and uncorrected TE90 (RSIrs TE90 ) to RSIrs from reference TEmin 1 (RSIrs TEmin1 ) and repeated TEmin 2 (RSIrs TEmin2 ). Calibration performance was evaluated with sensitivity, specificity and area under the ROC curve (AUC)., Results: Scaling factors for C 1 , C 2 , C 3 , and C 4 were estimated as 1.68, 1.33, 1.02, and 1.13, respectively. In non-csPCa cases, the 98th percentile of RSIrs TEmin2 and RSIrs TEmin1 differed by 0.27 ± 0.86SI (mean ± standard deviation), whereas RSIrs TE90 differed from RSIrs TEmin1 by 1.82 ± 1.20SI. After calibration, this bias was reduced to -0.51 ± 1.21SI, representing a 72% reduction in absolute error. For patients with csPCa, the difference was 0.54 ± 1.98SI between RSIrs TEmin2 and RSIrs TEmin1 and 2.28 ± 2.06SI between RSIrs TE90 and RSIrs TEmin1 . After calibration, the mean difference decreased to -1.03SI, a 55% reduction in absolute error. At the Youden index for patient-level classification of csPCa (8.94SI), RSIrs TEmin1 has a sensitivity of 66% and a specificity of 72%., Conclusions: The proposed linear calibration method produces similar quantitative biomarker values for acquisitions with different TE, reducing TE-induced error by 72% and 55% for non-csPCa and csPCa, respectively., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Tranexamic acid is a commonly used hemostatic agent with broad clinical uses across multiple specialties. Systemic toxicity is due to gamma-aminobutyric acid type A and glycine receptor competitive antagonism and has been reported by multiple routes, but toxicity after pulmonary administration via nebulization and BAL has not yet been described. A 44-year-old man with a history of congenital pulmonary arteriovenous malformations underwent routine bronchoscopy for hemoptysis. He received preprocedure nebulized tranexamic acid 500 mg three times daily for 48 h. An additional 1,000 mg was given via BAL for intraprocedural hemostasis. One hour after the procedure, he developed altered mental status, myoclonus, and hyperthermia, which was ultimately controlled with propofol and vecuronium. As the use of pulmonary tranexamic acid increases, toxicity from this agent should be considered. Dose reductions and alternate treatment modalities should be considered in patients with advanced age, arteriovenous malformations, and renal insufficiency., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Published by Elsevier Inc.)

Purpose: We aimed to estimate health state utility values (HSUVs) for the key health states found in opioid use disorder (OUD) cost-effectiveness models in the published literature., Methods: Data obtained from six trials representing 1,777 individuals with OUD. We implemented mapping algorithms to harmonize data from different measures of quality of life (the SF-12 Versions 1 and 2 and the EQ-5D-3 L). We performed a regression analysis to quantify the relationship between HSUVs and the following variables: days of extra-medical opioid use in the past 30 days, injecting behaviors, treatment with medications for OUD, HIV status, and age. A secondary analysis explored the impact of opioid withdrawal symptoms., Results: There were statistically significant reductions in HSUVs associated with extra-medical opioid use (-0.002 (95% CI [-0.003,-0.0001]) to -0.003 (95% CI [-0.005,-0.002]) per additional day of heroin or other opiate use, respectively), drug injecting compared to not injecting (-0.043 (95% CI [-0.079,-0.006])), HIV-positive diagnosis compared to no diagnosis (-0.074 (95% CI [-0.143,-0.005])), and age (-0.001 per year (95% CI [-0.003,-0.0002])). Parameters associated with medications for OUD treatment were not statistically significant after controlling for extra-medical opioid use (0.0131 (95% CI [-0.0479,0.0769])), in line with prior studies. The secondary analysis revealed that withdrawal symptoms are a fundamental driver of HSUVs, with predictions of 0.817 (95% CI [0.768, 0.858]), 0.705 (95% CI [0.607, 0.786]), and 0.367 (95% CI [0.180, 0.575]) for moderate, severe, and worst level of symptoms, respectively., Conclusion: We observed HSUVs for OUD that were higher than those from previous studies that had been conducted without input from people living with the condition., (© 2024. The Author(s).)

Background: Pathologic antibody mediated rejection (pAMR) evaluation and donor specific antibody (DSA) testing are recommended in the first year after heart transplantation (HTx) in adult patients. Whether DSA testing adds prognostic information to contemporary pAMR surveillance has not been fully studied., Methods: This was a single center study of consecutive endomyocardial biopsies (EMB) performed between November 2010 and February 2023 in adult HTx patients. The primary objective was to evaluate whether DSA testing contributes additional information to pAMR surveillance to better predict overall survival. Secondary endpoints included cardiac allograft dysfunction and loss., Results: A total of 6,033 EMBs from 544 HTx patients were reviewed for the study. The pAMR+/DSA+ group had significantly lower overall survival versus the pAMR-/DSA- group (hazard ratio [HR] = 2.63; 95% confidence interval [CI], 1.35-5.11; p c = 0.013). In the pAMR+/DSA+ group, patients with cardiac allograft dysfunction, compared to those without allograft dysfunction, had significantly lower overall and cardiac survival (p c < 0.001 for both). In contrast, pAMR+/DSA+ and pAMR-/DSA- patients without cardiac allograft dysfunction showed no difference in overall and cardiac survival. Primary graft dysfunction (PGD) was a novel risk factor for development of de novo DSAs (dnDSA) three weeks post-HTx (p = 0.007)., Conclusions: DSA testing as the primary surveillance method can identify high-risk pAMR+/DSA+ patients. Surveillance pAMR testing in the contemporary era may need to be reevaluated. Earlier DSA testing at 10-14 days post-HTx should be considered in PGD patients.

Context: Pain and symptom management at the end of life (EoL) can pose unique challenges, particularly when symptoms are refractory to conventional methods. Dexmedetomidine, originally approved for sedation in ventilated patients, has been demonstrated to be beneficial in pain management and palliative care settings by functioning as an alpha-2 agonist. Methods: A retrospective review of inpatient palliative care unit (IPU) records from January 2020 to December 2023 was conducted. Twenty-five adult patients receiving continuous dexmedetomidine for refractory pain at the EoL were identified. These patients were further evaluated for concurrent opioid, benzodiazepine, and chlorpromazine usage. Results: Patients experienced predominantly cancer-related pain, and had a median infusion duration of 5 days. Dexmedetomidine's initial dosing differed between the intensive care unit (ICU) and IPU settings. There was a trend toward a decreased opioid requirement 24 hours after initiation. Patients transferred from the ICU showed a progressive increase in opioid use. Conclusion: This study contributes to understanding dexmedetomidine's role in managing refractory symptoms at the EoL in the palliative care setting.

Objectives: Serum creatinine (SCr) is the primary biomarker for assessing kidney function; however, it may lag behind true kidney function, especially in instances of acute kidney injury (AKI). The objective of the work is to develop Nephrocast, a deep-learning model to predict next-day SCr in adult patients treated in the intensive care unit (ICU)., Materials and Methods: Nephrocast was trained and validated, temporally and prospectively, using electronic health record data of adult patients admitted to the ICU in the University of California San Diego Health (UCSDH) between January 1, 2016 and June 22, 2024. The model features consisted of demographics, comorbidities, vital signs and laboratory measurements, and medications. Model performance was evaluated by mean absolute error (MAE) and root-mean-square error (RMSE) and compared against the prediction day's SCr as a reference., Results: A total of 28 191 encounters met the eligibility criteria, corresponding to 105 718 patient-days. The median (interquartile range [IQR]) MAE and RMSE in the internal test set were 0.09 (0.085-0.09) mg/dL and 0.15 (0.146-0.152) mg/dL, respectively. In the prospective validation, the MAE and RMSE were 0.09 mg/dL and 0.14 mg/dL, respectively. The model's performance was superior to the reference SCr., Discussion and Conclusion: Our model demonstrated good performance in predicting next-day SCr by leveraging clinical data routinely collected in the ICU. The model could aid clinicians in in identifying high-risk patients for AKI, predicting AKI trajectory, and informing the dosing of renally eliminated drugs., Competing Interests: S.N., S.P.S., and A.M. are cofounders, advisors, and hold equity in Healcisio Inc, a predictive analytics startup. The terms of this arrangement have been reviewed and approved by the UC San Diego in accordance with its conflict-of-interest policies. A.M. is funded by the National Institutes of Health. A.M. reports income related to medical education from Livanova, Eli Lilly, Zoll, and Powell Mansfield. ResMed provided a philanthropic donation to UCSD. KS’s institution receives grant funding from the National Institute for Diabetes and Digestive and Kidney Disease; K.S.’s institution previously received grant funding from Teva Pharmaceuticals; K.S. previously consulted for Flatiron Health. L.A. serves as a clinical consultant for MediBeacon. Z.Y. serves as a clinical consultant for Takeda Pharmaceuticals., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Lack of patient diversity in clinical trial enrollment remains an obstacle to achieving equitable healthcare outcomes. Under-representation has resulted in non-generalizable clinical knowledge, inequitable access to treatment, and health disparities among minority and disadvantaged groups. A multidisciplinary panel was convened to consider the challenges of diverse patient accrual and provide actionable solutions to improve representation in clinical trials. The panel was comprised of participants with knowledge in gynecologic oncology and included physician, advanced practice nurse, patient navigator, patient advocate, and pharmaceutical industry representation. Focus was given to recruitment barriers for Asian and Hispanic patients. The panel identified several areas of concern, including explicit and implicit biases for the physician and care teams, language and cultural nuances, inadequate inclusion of family in the decision-making process, and under-representation of women in clinical trials. The panel also identified the important role patient navigators, nurses, and advanced practice providers have in patient recruitment from under-represented populations. The role of study sponsors, and global and regional initiatives, to address historic disparities in clinical trial recruitment were also considered critical. The actionable solutions proposed should enable study sponsors and clinical trial sites to achieve greater diversity in enrollment globally., Competing Interests: Competing interests: BP has received grants from Tesaro/GSK, Merck, Astra Zeneca, Karyopharm Therapeutics, Incyte, Toray, VBL Therapeutics, InxMed, Agenus, Clovis Oncology, Roche/Genentech, Mersana, Celsion/Immunon, I-Mab, Takeda, Onconova, Celgene, Sutro Biopharma, Novocure, Seagen, NRG Oncology, Duality Bio, Xencor, Immunogen, Eisai, Acrivon, and Alkermes; consulting fees from Tesaro/GSK, Astra Zeneca, Merck, Immunogen, GOG Foundation, Seagen, Lilly, Eisai, Signatera, Celsion, Sutro Biopharma, Imvax, Incyte, InxMed, Onconova Therapeutics, R-Pharm, Regeneron, and Duality Bio; honoraria from Bioascend, PERS, Vanium, Curio, OncLive, Yale University, and PeerView; support for attending meetings and/or travel from GOG Partners; participated on data safety monitoring boards (DSMBs) or advisory boards for Sutro Biopharma, Astra Zeneca, GOG Foundation, Celsion/Immunon, Toray, InxMed, Onconova, Imvaz, I-Mab, Tesaro/GSK, Merck, Mersana, Nuvation, and BioNTech; and served as SGO Clinical Practice Committee Chair, SGO Board of Directors, SGO COVID-19 Taskforce Co-chair, GOG Partners, and NYOB Society Second Vice President. PT has received grants (paid to the institution) from Merck and GSK; participated on DSMBs or advisory boards for Iovance, Astra Zeneca, Verastem, GSK, Seagen, Immunon, Immunogen, Mersana, Novocure, Zentalis, Caris, and Merck; and holds stock or stock options in Immunon. AM has received honoraria and travel fees from Foundation for Women’s Cancer and served as President of Endometrial Cancer Action Network for African Americans. KM has received consulting fees from Eisai. DC has received honoraria from Antibacterial Resistance Leadership Group (ARLG); grants from Duke University for COMET study (cancer) Patient Leadership Group, UCSF for STORMing Cancer Patient Advocate Team, and MD Anderson for PRECISION Patient Advisory Involvement Panel; consulting fees from SimBioSys, MaxisHealth, Health Literacy Media (HLM; as Patient Advisor), Apellis Pharmaceuticals, and Kinnate Biopharma; honoraria and travel support from HMP Education; support for travel from Agile Falcon Strategic Group, DGE Events, and Informa; participated on DSMBs for American Society for Clinical Oncology and on Patient Partner Council for Evidera; has a role on Executive Group for Metastatic Breast Cancer Alliance and a role as committee member for Alliance for Clinical Trials in Oncology; and received manuscript writing support from IQVIA through Regeneron. KL has received fees for participation on advisory boards for Astra Zeneca, Merck, and Eisai. MCM is an employee and stockholder of Incyte. BS has received consulting fees from Astra Zeneca, Clovis, GSK, Genentech, Lilly, Novartis, Gilead, Seagen, Karyopharm, Addy, Circulogene, GOG Foundation, Merck, Imvax, EQRx, and Nuvation; and honoraria from Seagen., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Purpose: Little is known about cancer-related cognitive impairments (CRCI) in women with metastatic breast cancer (MBC). The purpose of this study is to (1) comprehensively describe CRCI and any associated psychosocial and behavioral symptoms, (2) determine observable sociodemographic and clinical risk factors for CRCI, and (3) explore cognitive and psychosocial predictors of quality of life and social functioning in women living with MBC., Methods: Using a cross-sectional design, women with MBC completed assessments (objective and subjective measures of CRCI including 3 open-ended questions, measures of psychosocial and behavioral factors, and assessments of quality of life and social function), and data were analyzed using descriptive statistics, qualitative content analysis, correlation analyses, t tests, analysis of variance, and linear regression models., Results: Data from 52 women were analyzed. 69.2% of the sample reported clinically significant CRCI and 46% of the sample scored < 1 standard deviation below the standardized mean on one or more cognitive tests. Those with triple-negative MBC (compared to HER2+), recurrent MBC (compared to de novo), and no history of chemotherapy had worse subjective CRCI, and those without history of surgery and older age had worse objective CRCI. Subjective CRCI, but not objective CRCI, was significantly associated with quality of life and social functioning., Conclusion: Subjective and objective CRCI are likely a common problem for those with MBC. Subjective CRCI is associated with poorer quality of life and lower social functioning. Healthcare providers should acknowledge cognitive symptoms, continually assess cognitive function, and address associated unmet needs across the MBC trajectory., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Compare the real-world impact of fidaxomicin (FDX) and vancomycin (VAN) on Clostridioides difficile infection (CDI) recurrence in a high-risk patient population., Design: A retrospective, matched-cohort study evaluating hospitalized patients with CDI from January 1, 2016, to November 1, 2022, within a tertiary academic medical center., Patients: Adult patients with at least 1 prior CDI case who received either FDX or VAN for non-fulminant CDI while admitted, and had at least 1 additional risk factor for recurrence. Risk factors included age >70, solid organ or bone marrow transplant recipients, broad-spectrum antibiotic use within 30 days, or receipt of chemotherapy/immune-modulating agents within 30 days of admission. FDX and VAN patients were matched according to risk factors., Results: A total of 415 patient admissions were identified. After the exclusion of 92 patients for fulminant CDI, diarrhea from another cause, or use of VAN taper therapy, and 15 unmatched patients, 308 patient admissions were included (68 FDX and 240 VAN patients). There were no significant differences in 4-week recurrence (26% vs 23%; OR 1.1; P = .51), 90-day CDI readmission (29% vs 23%; P = .65), or 90-day all-cause readmission (54% vs 53%; P = .91). There was a significant 17% decrease in 90-day mortality associated with the use of FDX (OR .3; P = .04)., Conclusions: In a real-world high-risk patient population, the use of FDX compared to oral VAN did not result in decreased CDI recurrence within 4 weeks or fewer hospital readmissions within 90 days. Further research is needed to better assess the value of FDX in this patient population., Competing Interests: Y. G. received a grant from Merck. The rest of the authors report no conflicts of interest relevant to this article., (© Cambridge University Press 2024.)

The National Resident Matching Program (NRMP) for pain medicine fellowships marked its 10th anniversary in 2023, coinciding with growing discussions within the Association of Pain Program Directors (APPD) regarding the program's future in the context of a recent decline of applicants into pain medicine. This letter explores the rationale behind reassessing the NRMP's utility for pain medicine, examining historical and current trends, and considering the implications of withdrawing from the match. Despite a recent decline in applicants and an increase in unfilled positions, the APPD advocates for continued participation in the match. The match ensures equitable and stable recruitment, preventing the chaotic pre-match environment of competitive, early offers. Data from similar specialties highlight the pitfalls of non-match systems, such as increased applicant pressure and reduced program visibility. The APPD supports maintaining the NRMP match while implementing reforms like preference signaling to address evolving challenges. The APPD aims to preserve the match's benefits and ensure a stable future for pain medicine fellowship recruitment., Competing Interests: Competing interests: LK - institutional funding from FUSMObile, Averitas, Vertex – not relevant to paper., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: The author declares no conflicts of interest.

Peer review is an important component of any radiation oncology continuous quality improvement program. While limited guidelines exist, there is no consensus about how peer review should be performed, and large variations exist among different institutions. The purpose of this report is to describe our experience with peer review at a busy Radiation Oncology clinic and to evaluate the difference between prospective and retrospective peer review. We also performed a failure modes and effects analysis (FMEA) of the peer review process. Starting in 2015, every peer review session was tracked, including recommended changes to treatment plans. We reviewed the frequency, types and severity of these changes. A team of physicians and physicists conducted an FMEA of the peer review process. Between April 2015 and June 2020, a total of 3,691 patients were peer-reviewed. Out of those, 1,903 were prospective reviews (51.6%). Plans reviewed before treatment were almost 4.5 times more likely to be changed by peer review than those reviewed after the start of treatment (0.9% vs 0.2%). Plan changes after the start of treatment had a higher severity than changes prior to the start of treatment. FMEA identified several critical components of peer review. While there is no national standard for peer review, it is evident that prospective peer review is preferable. There may be a subconscious reluctance to change plans already underway, which could be a barrier to improving plans with the peer review process. Rather than reviewing in a group setting, it would be ideal to individually assign review tasks that are embedded in the clinical flow, assuring prospective review for all patients prior to final physician approval. Individual review rather than group review may be more candid, due to interpersonal concerns about publicly disagreeing with colleagues., Competing Interests: Conflict of Interest None, (Copyright © 2024 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: Minimally invasive single position lateral ALIF at L5-S1 with simultaneous robot-assisted posterior fixation has technical and anatomic considerations that need further description., Methods: This is a retrospective case series of single position lateral ALIF at L5-S1 with robotic assisted fixation. End points included radiographic parameters, lordosis distribution index (LDI), complications, pedicle screw accuracy, and inpatient metrics., Results: There were 17 patients with mean age of 60.5 years. Eight patients underwent interbody fusion at L5-S1, five patients at L4-S1, two patients at L3-S1, and one patient at L2-S1 in single lateral position. Operative times for 1-level and 2-level cases were 193 min and 278 min, respectively. Mean EBL was 71 cc. Mean improvements in L5-S1 segmental lordosis were 11.7 ± 4.0°, L1-S1 lordosis of 4.8 ± 6.4°, sagittal vertical axis of - 0.1 ± 1.7 cm°, pelvic tilt of - 3.1 ± 5.9°, and pelvic incidence lumbar-lordosis mismatch of - 4.6 ± 6.4°. Six patients corrected into a normal LDI (50-80%) and no patients became imbalanced over a mean follow-up period of 14.4 months. Of 100 screws placed in lateral position with robotic assistance, there were three total breaches (two lateral grade 3, one medial grade 2) for a screw accuracy of 97.0%. There were no neurologic, vascular, bowel, or ureteral injuries, and no implant failure or reoperation., Conclusion: Single position lateral ALIF at L5-S1 with simultaneous robotic placement of pedicle screws by a second surgeon is a safe and effective technique that improves global alignment and lordosis distribution index., (© 2023. The Author(s).)

Introduction: Immune checkpoint inhibitors (ICIs) are linked with various cutaneous side effects ranging from mild to life-threatening. Herein, we present a unique case of palmar-plantar erythrodysesthesia (PPE) in a patient treated with atezolizumab., Case Report: A 72-year-old white man was diagnosed with Tumor, node, metastasis (TNM) stage IIIA lung adenocarcinoma in November 2022. He underwent right lower lobectomy and mediastinal lymphadenectomy followed by adjuvant cisplatin-pemetrexed. As of May 2023, he did not have any evidence of relapse. He then started switch maintenance therapy with atezolizumab. At 24 weeks, the patient developed erythematous palmar skin lesions, followed by blisters and peeling of both palms, which were associated with swelling and pain, consistent with grade 2 PPE., Management and Outcome: Causality assessment between nivolumab and PPE via adverse drug reaction probability scale revealed a score of 5. Atezolizumab was continued, and he started on a cream consisting of trolamine and 75% water to palms twice daily. A follow-up visit 6 weeks later showed significant improvement in symptoms and appearance of palmar lesions., Discussion: Cutaneous side effects are commonly seen with ICIs. PPE is a common dermatologic toxicity of certain tyrosine kinase inhibitors (TKIs). This effect has been previously reported with combination therapies consisting of an ICI plus a TKIs, but not with ICI monotherapy. Awareness of this potential side effect of ICIs would prevent unnecessary work-up, and lead to its prompt diagnosis and treatment., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The nursing work environment is often stressful and can lead to burnout. The use of humor may help nurses adapt and cope. Although most would agree that, in general, humor can help build camaraderie and ease tense situations, little is known about how nurses use humor in their professional lives., Purpose: The study's main purpose was to explore how humor is used and perceived by nurses in the workplace., Methods: A sample of LPNs, RNs, and advanced practice RNs was recruited in the United States. Participants were interviewed via the videoconferencing platform Zoom. Data from the video recordings, audio transcripts, and investigators' field notes were analyzed using reflexive thematic analysis., Results: Sixteen nurses were interviewed about their use of humor, whether intentional or spontaneous, in the workplace. Three main themes were identified: entertainment , influencing others , and well-being . Participants reported using humor with self and others, including patients, families, and colleagues. Reported benefits include emotional regulation, relationship building, and work enjoyment. Some participants noted feeling insecure over when and whether the use of humor was "appropriate.", Conclusions: The results indicate that nurses' use of humor in the workplace had many benefits. Participants reported that humor could relieve tension, create bonds and strengthen relationships, and enhance both learning and work environments. Many recognized that humor can also be maladaptive and harmful, and that sensitivity and caution are part of using humor skillfully. Still, the benefits of humor appear to outweigh the risks. We conclude that humor is a useful tool nurses can and should use to optimize their nursing experience., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Obstructive sleep apnea (OSA) is strongly associated with obesity. While the relationship between weight reduction and apnea-hypopnea index improvement has been documented, to our knowledge, it has not been quantified adequately. Therefore, this study aimed to quantify the relationship between weight reduction and AHI change., Methods: A systematic literature search was performed using meta-analyses (PRISMA) guidelines for studies reporting AHI and weight loss in people with obesity/overweight and OSA between 2000 and 2023. A linear and quadratic model (weighted by treatment arm sample size) predicted percent change from baseline AHI against mean percent change from baseline weight. The quadratic term was statistically significant (P < 0.05), so the quadratic model (with 95 % prediction interval) was used., Results: The literature search identified 27 studies/32 treatment arms: 15 using bariatric surgery and lifestyle intervention each and 2 using pharmacological interventions. Included studies were ≥3 months with weight intervention and participants had AHI ≥15/h. Weight reduction in people with OSA and obesity was associated with improvements in the severity of OSA. BMI reduction of 20 % was associated with AHI reduction of 57 %, while further weight reduction beyond 20 % in BMI was associated with a smaller effect on AHI. As the prediction intervals are relatively wide, a precise relationship could not be conclusively established., Conclusion: The degree of AHI index improvement was associated with the magnitude of weight reduction. The model suggests that with progress in weight reduction beyond 20 %, the incremental decrease in BMI appeared to translate to a smaller additional effect on AHI., Competing Interests: Declaration of competing interest Atul Malhotra receives funding from the NIH. He reports income related to medical education from Zoll, Livanova, Eli Lilly and Company, and Jazz. ResMed provided a philanthropic donation to UCSD. Cory R Heilmann, Julia P. Dunn, Kushal K. Banerjee, Mathijs C. Bunck, and Josef Bednarik are employees and shareholders of Eli Lilly and Company., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of competing interest Dr. Chawla is currently the chief medical officer of Silver Creek Pharmaceuticals. Previously, Dr. Chawla was CMO at La Jolla Pharmaceutical Company, where he holds patent equity as an inventor on patents for “Angiotensin II Alone Or In Combination For The Treatment Of Hypotension” (US Patent 9,220,745, US Patent Application 14/941301). Dr. Ince is the CSO of Active Medical BV, Leiden, The Netherlands, a company that provides devices (OxyCam), software (MicroTools), education (Microcirculation Academy), and services related to clinical microcirculation. All other authors declare that they have no conflict of interest.

Purpose: This cross-sectional prospective study measured utility values of upper eyelid dermatochalasis to quantify its impact on quality of life and assess cost-effectiveness of upper blepharoplasty., Methods: Utility of dermatochalasis was assessed using the standard reference gamble and time trade-off methods, with dual anchor points of perfect eye function and perfect health. The utility value obtained was used to create a Markov model and run a cost-effectiveness analysis of blepharoplasty as a treatment for dermatochalasis while utilizing the societal perspective., Results: One hundred three patients with dermatochalasis recruited from an urban outpatient ophthalmology clinic completed the utility survey. The authors determined utility values for dermatochalasis ranging from 0.74 to 0.92 depending on the measurement method (standard reference gamble/time trade-off) and anchor points. The cost-effectiveness analysis yielded an incremental cost-effectiveness ratio of $3,146 per quality-adjusted life year, well under the conventional willingness-to-pay threshold of $50,000 per quality-adjusted life year. Probabilistic sensitivity analysis with Monte Carlo simulation demonstrated that blepharoplasty would be cost-effective in 88.1% of cases at this willingness-to-pay threshold., Conclusions: Dermatochalasis has an impact on quality of life that is significantly associated with level of perceived functional impairment. Rising health care costs have underscored the importance of providing value-based treatment to patients, and the results of this study suggest that blepharoplasty is a cost-effective treatment option for symptomatic bilateral upper eyelid dermatochalasis., Competing Interests: CYL: site principal investigator for a Horizon Therapeutics-sponsored clinical trial and receives royalties from Wolter Kluwers Health. BSK: former consultant with Horizon Therapeutics and receives royalties from Elsevier, Ltd. DOK: former consultant with Horizon Therapeutics and receives royalties from Elsevier, Ltd. All other authors have no conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Objective: As the majority of oropharyngeal squamous cell carcinoma (OPSCC) is diagnosed in males, outcomes among females are not well-characterized. We identify sex-specific factors in OPSCC to refine female prognostication., Study Design: Retrospective cohort., Setting: National Cancer Database (NCDB)., Methods: OPSCC cases from the 2004 to 2019 NCDB were identified. Sociodemographic, clinical, and treatment characteristics (including timing between diagnosis and treatment administration) were compared between sexes. Multivariable Cox proportional hazard regression models were constructed to characterize survival in overall and female-only cohorts. Similar multivariable binomial logistic regression and survival models were constructed to assess odds of treatment delays and their effects on survival, respectively., Results: A total of 192,973 OPSCC patients were identified; 36,695 (19%) were female. Females had more human papillomavirus (HPV) negative, lower clinical T and N stage, and higher comorbidity disease. Females experienced lower survival in HPV negative (hazard ratio, HR = 1.11, P < .001) but not HPV-positive disease. Females were more likely to have any treatment initiated over the median of 28 days (odds ratio, OR = 1.04, P = .014) or delays in adjuvant radiotherapy initiation over 6 weeks (OR = 1.11, P = .032). Treatment delay over 60 days (HR = 1.17, P = .016) and delay in adjuvant therapy initiation (HR = 1.24, P = .02) were associated with worse survival among females., Conclusion: In one of the largest analyses of OPSCC, females had poorer survival than males, specifically in HPV-negative disease, despite presentation with less advanced disease. Notably, delays in any treatment initiation and adjuvant radiotherapy initiation were more likely in HPV-negative women and associated with worse survival, highlighting potential systemic weaknesses contributing to poor prognosis among females., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Oxytocin (OT) is a neuropeptide broadly implicated in social relationships and behavior. OT also exerts antinociceptive and pain-reducing effects in both humans and rodents. Recent research in rodents demonstrates that these effects can be peripheral and local. In human studies, intravenous OT has reduced visceral pain, and subcutaneous injection of OT has reduced postsurgical pain. However, the local effects of subcutaneous OT on experimental pain have not been studied. We conducted a 2-session crossover study during which healthy adults received a subcutaneous injection of synthetic OT (4 mcg/2 mL) or saline placebo (isotonic saline 2 mL), in a randomized and double-blinded manner. Eighteen participants completed full study procedures. We hypothesized that 10 minutes after injection, OT would reduce measures of acute mechanical pain, pressure pain, and heat pain perception. Subcutaneous OT significantly reduced ratings of heat pain intensity and unpleasantness (both P < .01), but did not alter mechanical pain, pressure pain, or heat pain threshold (all P > .05). Changes in heat pain were observed only on the injected arm and not on the contralateral arm, confirming a localized mechanism. These findings confirm the ability of OT in or near the skin to modulate nociceptive processes in cutaneous tissues in human adults, opening exciting avenues for further mechanistic research as well as potential clinical applications for acute pain. PERSPECTIVE: This randomized-controlled trial showed that a subcutaneous injection of OT could reduce perception of heat pain tested with a thermode. OT did not alter mechanical or pressure pain or thresholds for perceiving heat pain. These findings are relevant to scientists and clinicians seeking nonaddictive local drug treatments for pain., (Published by Elsevier Inc.)

Purpose: The purpose of this study is to investigate the impact of Mayo Adhesive Probability (MAP) score and body mass index (BMI) on renal function decline after robotic assisted partial nephrectomy (RAPN)., Methods: We queried our prospective database for patients who underwent RAPN between January 2018 and December 2023. Outcomes were development of de novo CKD-S3 (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m 2 ). Multivariable analysis (MVA) via Cox regression identified predictors for CKD-S3. Kaplan-Meier Analyses was fitted for survival assessment. Finally, multivariable linear regression was utilized to identify predictors of delta eGFR at last follow-up (preoperative eGFR-last eGFR)., Results: Two-hundred fifty-eight patients were analysed (obese n  = 49 [19%]; MAP score 0-2 = 135 [52.33%]; MAP score 3-5 = 123 [47.6%]) with a median follow-up of 33 (IQR 20-42) months. MVA revealed, high MAP score (HR 2.29, p  = 0.019), increasing RENAL score (HR 1.26, p  = 0.009), increasing age (HR 1.04, p  = 0.003), obesity (HR 2.38, p  = 0.006) and diabetes mellitus (HR 2.38, p  = 0.005) as associated with increased risk of development of CKD-S3, while trifecta achievement was not ( p  = 0.63). Comparing low MAP score versus high MAP score 4-year CKD-S3 free survival was 87.8% versus 56.1% ( p  < 0.001). Multivariable linear regression showed that high MAP score (coefficient 6.64, p  = 0.001) and BMI (coefficient 0.51, p  = 0.011) were significantly associated with increased delta eGFR at last follow up., Conclusions: MAP score and increasing BMI are predictor for long term renal functional detrimental. These insights may call consideration for closer follow-up or greater medical scrutiny prior surgery in obese patients and with elevated MAP score. Further investigations are requisite., Competing Interests: There are no potential competing interests to declare., (© 2024 The Author(s). BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Objectives: Up to a quarter of pregnant individuals with systemic lupus erythematosus (SLE) have small for gestational age (SGA) infants. We aimed to characterize placental pathology associated with SGA infants in SLE., Methods: We retrospectively analyzed SLE deliveries with placental analysis at UCSD from 11/2018-10/2023, comparing SLE pregnancies resulting in SGA to those that did not, and additionally, to matched pregnancies with SGA but without SLE., Results: Placental analysis was available only for 28/70 (40%) SLE deliveries, which had high rates of adverse outcomes (75%). All exhibited at least one histopathologic abnormality. Key findings distinguishing 12 SLE placentas resulting in SGA infants (vs.16 without) included small placental disc for gestational age (100% vs 56%, p= 0.01), placental disc infarct (50% vs 6%, p= 0.02), and increased perivillous fibrin deposition (PVFD, 58% vs 0%, p= 0.001). All seven SLE placentas with increased PVFD resulted in SGA infants. Compared with matched non-SLE pregnancies with SGA (n = 36), the only distinguishing placental lesion was a higher prevalence of increased PVFD in SLE-associated SGA (58% vs 22%, p= 0.03)., Conclusion: The higher prevalence of increased PVFD in placentas of SLE-associated SGA may indicate a specific mechanism of placental injury leading to SGA in this context. Thus, its presence, particularly in context of SGA, should prompt providers to screen for an underlying autoimmune disease, including SLE. Systematic placental examination in context of SLE and associated autoimmune diseases could help evaluate responses to existing therapies, comparative studies of novel therapies, and correlation to adverse outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: With the recent Food & Drug Administration (FDA) approval of cellular therapy that requires product manipulation prior to administration in combination with a short stability window, the need was identified for local dose preparation within the pharmacy rather than the off-site stem cell processing laboratory. This approval gave rise to assessment of regulatory standards surrounding cellular therapy, evaluation and revision of current standard operating procedures and policies with formal process validation, assessment of occupational exposure mitigation and safety considerations, and development of staff training and education., Objective: To describe and provide insight into the stepwise process of FACT validation and onboarding of commercially available cellular therapy products that require sterile compounding manipulation within a pharmacy prior to administration., Discussion: A multidisciplinary effort is required to attain FACT certification and implement pharmacist compounding of cellular therapy products. 1 Local preparation within a pharmacy facilitates a sound operational workflow and provides a pathway to perform aseptic manipulations of cellular therapy products safely and efficiently., Conclusion: Safe and successful administration of cellular therapies handled and compounded by pharmacy department staff along with program validation requires a preemptive review utilizing a multidisciplinary approach for process development. This manuscript will provide a foundation based on consistency and transparency in effective cellular therapy sterile compounding and aseptic manipulation, proper handling and disposal procedures, increased communication through creation and optimization of treatment plans and order-sets, standardized medical center staff education, and development of policies and standard operating procedures for the entire health care team., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Benzodiazepines are commonly prescribed medications frequently linked to instances of abuse and overdose. Historically, FDA-cleared benzodiazepine urine immunoassays cross-react poorly with glucuronidated benzodiazepine metabolites, leading to false negatives. Clinical laboratories have addressed this deficiency by creating laboratory-developed tests (LDTs) that incorporate a beta-glucuronidase hydrolysis step to increase the clinical sensitivity of these assays., Methods: Performance characteristics of 2 FDA-cleared benzodiazepine urine immunoassays (Benzodiazepines Plus, no glucuronidase and Benzodiazepines II, with glucuronidase; Roche Diagnostics) and a previously described benzodiazepine immunoassay LDT (with glucuronidase) were evaluated using 258 clinical urine specimens. The positive immunoassay cutoff was set at 200 ng/mL of nordiazepam and results were compared to an LC-MS/MS benzodiazepine LDT. Clinical sensitivity, specificity, precision, and immunoassay cross-reactivity were determined for all 3 immunoassays., Results: The Benzodiazepines II and LDT immunoassays exhibited greater clinical sensitivity (100% and 95.2%) compared to the Benzodiazepines Plus assay (66.7%). Clinical specificity of 100% was observed for all 3 assays. Immunoassay response of the Benzodiazepines II assay was greater across the range of concentrations tested (100-1000 ng/mL) relative to the other immunoassays and was the most sensitive immunoassay for the detection of lorazepam glucuronide., Conclusions: The Benzodiazepines II immunoassay demonstrated the greatest clinical and analytical sensitivity compared to the Benzodiazepines Plus and LDT immunoassays. The incorporation of beta-glucuronidase was crucial, as the Benzodiazepines II and LDT immunoassays demonstrated superior clinical sensitivity when compared to the Benzodiazepines Plus immunoassay that does not incorporate a beta-glucuronidase hydrolysis step., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Many patients with cancer use cannabis to help alleviate untreated cancer symptoms and side effects., Methods: We examined associations of perceived benefits and risks and postdiagnosis cannabis use in a weighted sample of adult cancer survivors through a 1-time survey. Fifteen perceived cannabis use benefits and 19 perceived risks were operationalized as both summary scores and report of any benefits or risks. Survey-weighted logistic regression provided covariate-adjusted odds of postdiagnosis cannabis use for each benefit-risk measure., Results: Among the weighted population of 3785 survivors (mean [SD] age = 62.2 [13.5] years), one-third used cannabis after diagnosis. Perceiving any benefits increased the odds of postdiagnosis cannabis use more than 500%, and perceiving any risks lowered the odds by 59%. Each SD increase in endorsed benefits doubled the odds of postdiagnosis cannabis use, while each SD increase in endorsed risks reduced the odds by 36%., Conclusion: An accurate understanding of benefits and risks is critical for informed decision making., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The benefits of cannabis in symptom management among cancer survivors are widely acknowledged; however, patterns of cannabis use by cancer stage at diagnosis are unknown., Methods: Here, we examined the association between cancer stage at diagnosis and consideration of cannabis use since diagnosis. We analyzed cross-sectional survey data from 954 cancer survivors, weighted to be representative of a National Cancer Institute-Designated Comprehensive Cancer Center's patient population. We used survey-weighted multivariable logistic regression to examine the association between cancer stage at diagnosis (advanced [III/IV] versus non-advanced [I/II]) and consideration of cannabis use (yes versus no) since diagnosis., Results: Sixty percent of the population was diagnosed with non-advanced stages of cancer, and 42% had considered using cannabis since diagnosis. The odds of consideration of cannabis use were 63% higher (odds ratio = 1.63, 95% confidence interval = 1.06 to 2.49) among cancer survivors diagnosed at stages III/IV than among those diagnosed at stages I/II., Conclusion: Cancer stage may be a predictor of consideration of cannabis use after diagnosis., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)