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Background: Cancer rehabilitation and exercise oncology (CR/EO) have documented benefits for people living with and beyond cancer. The authors examined proximity to CR/EO programs across the United States with respect to population density, race and ethnicity, socioeconomic status, and cancer incidence and mortality rates. Methods: This cross‐sectional study was conducted in 2022–2023. Online searches were initiated to identify CR/EO programs. Geocoding was used to obtain latitudinal and longitudinal geospatial coordinates. Demographic data were abstracted from the 2020 5‐year American Community Survey. Cancer incidence and mortality data were obtained from the Centers for Disease Control and Prevention. US 2013 Rural‐Urban Continuum Code (RUCC) classification was used to define counties as either urban (RUCC 1–3) or rural (RUCC 4–9). Multivariable logistic regression was used to evaluate the association between being far from a program and census‐tract level factors. Results: In total, 2133 CR/EO programs were identified nationwide. The distance from a program increased with decreasing population density: rural tracts were 17.68 ± 0.24 miles farther from a program compared with urban tracts (p <.001). Program proximity decreased as the neighborhood deprivation index increased (p <.001). Exercise oncology programs were less common than cancer rehabilitation programs in tracts with a larger proportion of minority residents (p <.001). Conclusions: Prior research has documented that underrepresented populations have worse cancer‐related symptoms and higher cancer mortality. Herein, the authors document their findings that these same populations are less likely to have proximity to CR/EO programs, which are associated with improved cancer‐related symptoms and cancer mortality outcomes. To realize the positive outcomes from CR/EO programming, efforts must focus on supporting expanded programming and sustainable payment for these services. A search for exercise oncology and rehabilitation programs across the United States identified 2133 programs. Geographic proximity to these programs varied by rural versus urban geography, race and ethnicity, and socioeconomic status. [ABSTRACT FROM AUTHOR]

Background: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. Objectives: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. Methods: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super‐categories (e.g. 'benign') and cellular/tissue‐differentiation categories (e.g. 'melanocytic'), and appended with pertinent‐modifiers and synonyms. These terms were evaluated using a modified‐Delphi consensus approach. Experts from the International‐Skin‐Imaging‐Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. Results: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign‐category terms, 6/140 (4%) malignant‐category terms and 6/13 (46%) indeterminate‐category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super‐categories and 41 cellular/tissue‐differentiation categories. Conclusions: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon. [ABSTRACT FROM AUTHOR]

Background: X‐linked dystonia‐parkinsonism (XDP), a neurodegenerative movement disorder endemic to the Philippines, is primarily investigated in patients from Panay Island and the Greater Manila area. However, individuals residing in geographically distant regions may exhibit different clinical or genetic characteristics compared to those documented in earlier reports. Objective: The aim was to investigate the relationship of XDP clinical features in a Mindanao cohort with modifiers of age at onset (AAO) variability and utilization of a previously reported AAO model. Methods: We investigated clinical and genetic features in 27 XDP patients from southern Mindanao. In all patients, we genotyped the 4 polymorphisms linked to AAO. Results: The XDP‐relevant hexanucleotide repeat number significantly correlated with AAO in the 27 patients and explained about 68% of AAO variability. There is no statistical difference between the predicted and actual AAO. Conclusion: The AAO model may provide reliable predictions by employing the effect of XDP genetic modifiers of AAO variability. [ABSTRACT FROM AUTHOR]

Environmental strategy research has often used organizational interpretation as a key lens for understanding how firms engage in sensemaking around natural environmental issues and environmental performance. This work has rarely empirically tested the proposed relationships of organizational interpretation in firms' sensemaking around environmental issues nor the relationship between firms' environmental sensemaking and environmental performance. We empirically test this relationship, capturing environmental sensemaking through computer‐aided text analysis (CATA) of published sustainability reports, and environmental performance with the Trucost environmental dataset. Mixed‐effects general linear modeling on a bespoke longitudinal dataset of 117 publicly traded companies from 2005 to 2018 reveals the three stages of the organization interpretation model of sensemaking—scanning, interpreting, and responding—align as expected. We also find firms' environmental scanning relates with year‐over‐year improvement in environmental performance, yet environmental interpreting correlates with worsening environmental performance. Additionally, larger firms and firms in industries with high carbon emissions gather more environmental data and exhibit more extensive environmental interpreting. This research provides insight for scholars by testing environmental sensemaking and exploring the boundary conditions of sensemaking and performance, and for practitioners and policymakers by offering a new framework for analyzing and interpreting sustainability reports and corporate environmental performance. [ABSTRACT FROM AUTHOR]

This single‐center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post‐transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10% vs. 7%) and clinical rejection (21% vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24–24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection. [ABSTRACT FROM AUTHOR]

Endothelial‐to‐mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator‐Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia‐exposed mouse lungs, human PAECs, and in induced‐EndoMT cells. Etv2+/− mice spontaneously developed PH and right ventricular hypertrophy (RVH), associated with increased EndoMT markers and decreased EC markers. Interestingly, chronic hypoxia exacerbated right ventricular systolic pressure and RVH in Etv2+/− mice. PPARγ transcriptionally activates the ETV2 promoter. Consistently, while mice overexpressing endothelial PPARγ increases the expression of ETV2 and endothelial markers with reduced EndoMT markers, endothelial PPARγ KO mice show decreased ETV2 expression and enhanced EndoMT markers. Inducible overexpression of ETV2 under induced‐EndoMT cell model reduces number of cells with mesenchymal morphology and decreases expression of mesenchymal markers with increased EC makers, compared to control. Therefore, our study suggests that PPARγ‐ETV2 signaling regulates PH pathogenesis through EndoMT. [ABSTRACT FROM AUTHOR]

Objective: Evaluate utility of postoperative phosphate and calcium/phosphate ratio (Ca/P) as surrogates for parathyroid hormone (PTH) following total thyroidectomy. Study Design: Retrospective cohort study. Setting: Tertiary care hospital. Methods: We retrospectively reviewed patients 18 years or older who underwent total thyroidectomy in a tertiary care hospital by a single surgeon from 2015 through 2021. Patients with incomplete data, pre‐existing hypoparathyroidism, vitamin D deficiency, or renal failure were excluded. All patients had PTH drawn within 4 hours of surgery and serum calcium, albumin, and phosphate levels on postoperative Day 1. Corrected calcium was used to calculate a Ca/P. Receiver operating characteristic (ROC) curves were generated to compare phosphate level or Ca/P with PTH. Each possible surrogate was assessed relative to PTH cutoffs of less than 5, 10, 15, and 20 pg/mL. A good screening test was defined as having an area under the curve (AUC) greater than 0.8. Results: A total of 185 patients underwent total thyroidectomy with 1 fellowship‐trained otolaryngologist. Most patients were female (62%), median age 48 years. Most surgeries were performed for cancer (68%). Six (3.2%) patients required IV calcium supplementation and 2 (1.1%) required readmission for symptomatic hypocalcemia. ROC curves comparing phosphate and Ca/P to PTH at the listed cutoffs demonstrated AUC ranging from 0.55 to 0.66 and 0.61 to 0.79, respectively. None met the threshold for a good screening test. Conclusion: Postoperative phosphate and Ca/P ratio are not surrogates for PTH levels following total thyroidectomy. More research is needed to identify cost‐effective strategies for postoperative calcium monitoring in patients undergoing total thyroidectomy. Level of evidence: Retrospective cohort study. [ABSTRACT FROM AUTHOR]

Background: Alternate complement dysregulation postrenal transplantation can result in thrombotic microangiopathy (TMA). There is a scarcity of data regarding outcomes based on the timing of TMA post‐transplant, coupled with a lack of follow‐up biopsy findings post TMA diagnosis. This study aims to assess allograft and patient outcomes in individuals developing early TMA, defined within 4 months post‐transplantation, and explore any differences in follow‐up surveillance biopsies compared to a non‐TMA group. Design: This is a single center retrospective study between January 1, 2002 and October 10, 2019. Patients who developed TMA within 4 months post‐transplantation were compared to a propensity matched non‐TMA group. Results: Thirty‐one patients developed TMA within 4 months of renal transplantation. Index TMA biopsy featured noticeable glomerular, and vascular lesions along with acute tubular injury. Four‐month surveillance biopsy showed significant glomerulitis, transplant glomerulopathy and chronic interstitial fibrosis as compared to non‐TMA group. However, at 1 year, these differences were no longer significant. There was no significant difference in patient survival (TMA vs. non‐TMA, p = 0.083); however, death censored graft survival was significantly lower in the TMA group (p < 0.001). TMA patients had a significantly lower estimated glomerular filtration rate at 4 months and at 1 year as compared to the non‐TMA group. Conclusion: Early onset TMA post renal transplant leads to decreased renal function and lower graft survival. Early recognition and prompt treatment may help in reducing the adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: X‐Linked dystonia‐parkinsonism (XDP) is an adult‐onset neurodegenerative disorder characterized by rapidly progressive dystonia and parkinsonism. Mosaic Divergent Repeat Interruptions affecting motif Length and Sequence (mDRILS) were recently found within the TAF1 SVA repeat tract and were shown to associate with repeat stability and age at onset in XDP, specifically the AGGG [5′‐SINE‐VNTR‐Alu(AGAGGG)2AGGG(AGAGGG)n] mDRILS. Objective: This study aimed to investigate the stability of mDRILS frequencies and stability of (AGAGGG)n repeat length during transmission in parent–offspring pairs. Methods: Fifty‐six families (n = 130) were investigated for generational transmission of repeat length and mDRILS. The mDRILS stability of 16 individuals was assessed at two sampling points 1 year apart. DNA was sequenced with long‐read technologies after long‐range polymerase chain reaction amplification of the TAF1 SVA. Repeat number and mDRILS were detected with Noise‐Cancelling Repeat Finder (NCRF). Results: When comparing the repeat domain, 51 of 65 children had either contractions or expansions of the repeat length. The AGGG frequency remained stable across generations at 0.074 (IQR: 0.069–0.078) (z = −0.526; P = 0.599). However, the median AGGG frequency in children with an expansion (0.072 [IQR: 0.066–0.076]) was lower compared with children with retention or contraction (0.080 [IQR: 0.073–0.083]) (z = −0.007; P = 0.003). In a logistic regression model, the AGGG frequency predicted the outcome of either expansion or retention/contraction when including repeat number and sex as covariates (β = 80.7; z‐score = 2.63; P = 0.0085). The AGGG frequency varied slightly over 1 year (0.070 [IQR: 0.063–0.080] to 0.073 [IQR: 0.069–0.078]). Conclusions: Our results show that a higher AGGG frequency may stabilize repeats across generations. This highlights the importance of further investigating mDRILS as a disease‐modifying factor with generational differences. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Objective: The primary objective of this study was to evaluate oncologic outcomes of all published cases of supracricoid partial laryngectomy (SCPL) performed in the United States. The secondary objective was to assess the functional outcomes associated with this procedure. Review Methods: A systematic review of PubMed, SCOPUS, and Embase for all English‐language studies pertaining to SCPL performed in the United States was conducted until August 2021. Primary outcomes included disease‐specific survival (DSS), overall survival, and local recurrence rate. Secondary outcomes included larynx preservation rate, gastrostromy tube dependency, days to gastrostomy tube removal, decannulation rate, and days to decannulation. Results: A total of six studies were included in the analysis. A total of 113 patients (58.5%) underwent SCPL surgery as a primary treatment method whereas 80 patients (41.5%) underwent SCPL as salvage surgery. The 5‐year DSS rates were 87.8% and 100% for primary and salvage procedures, respectively. Approximately 10.3% of patients undergoing a salvage SCPL procedure experienced a local recurrence whereas only 1.85% of primary SCPL procedures resulted in local recurrence. The rates of decannulation following primary and salvage SCPL were 92.7% and 88.1%, respectively. With regard to swallowing, primary and salvage SCPL procedures demonstrated comparably low postoperative gastrostomy tube dependency rates of 3.66% and 4.76%, respectively. Conclusions: SCPL performed in the United States is an effective surgical technique that produces excellent outcomes in qualifying patients, thus validating its viability as an organ‐preserving surgical alternative. Laryngoscope, 134:3003–3011, 2024 [ABSTRACT FROM AUTHOR]

Objective(s): Despite advancements in imaging techniques and cytological analysis, plunging ranula remains a challenging surgical, radiologic, and pathologic phenomenon. Of the 18 patients we evaluated at our institution, we highlight three cases that illustrate the high rate of misleading imaging and cytological results when assessing plunging ranula. Methods: Imaging results, biopsy findings, operative techniques, and pathological reports were reviewed from patients who had either a preoperative or postoperative diagnosis of ranula and underwent surgery by a single head and neck surgeon at a tertiary care center. Results: Of the 18 identified patients, computed tomography was correct on preoperative imaging 73% of the time and magnetic resonance imaging was correct on preoperative imaging 71% of the time. Two patients underwent preoperative ultrasound and their ultrasound reports did not accurately diagnose the presence of a ranula. Two patients underwent preoperative fine needle aspiration biopsy due to inconclusive preoperative imaging, in which results suggested either a ranula or epidermal cyst. Both ultimately did not match the final pathology. Three of eighteen patients (17%) underwent an inappropriate initial surgery due to incorrect imaging diagnoses and/or biopsy findings. Conclusion: Despite use of preoperative modalities to distinguish plunging ranula from other cystic floor of mouth lesions, surgeons must be aware that no workup modality is fully precise. The potential for revision surgery must be included in all preoperative discussions for presumed plunging ranula. Level of Evidence: 4 Laryngoscope, 134:2689–2696, 2024 [ABSTRACT FROM AUTHOR]

This article discusses a novel approach to demonstrating supplemental margins during oncologic resection using iPad annotation of 3D surgical models. Surgeons and pathologists used the Procreate® application on an iPad to annotate virtual models of surgical defects and resection specimens in 3D. This method improves interdepartmental communication and provides visual documentation of surgical steps taken to address at-risk margins. The study demonstrates that using Procreate® for annotation improves efficiency and legibility, establishing a bidirectional exchange of visual information between surgeon and pathologist. This technique has the potential to enhance surgical outcomes and reduce the need for additional treatment. [Extracted from the article]

Background: X‐linked dystonia‐parkinsonism (XDP) is a rare movement disorder characterized by profound neurodegeneration in the basal ganglia. The molecular consequences and the bioenergetic state of affected individuals remain largely unexplored. Objectives: To investigate the bioenergetic state in male patients with XDP and female carriers using 31phosphorus magnetic resonance spectroscopy imaging and to correlate these findings with clinical manifestations. Methods: We examined the levels of high‐energy phosphorus‐containing metabolites (HEP) in the basal ganglia and cerebellum of five male patients with XDP, 10 asymptomatic female heterozygous carriers, and 10 SVA‐insertion‐free controls. Results: HEP levels were reduced in the basal ganglia of patients with XDP (PwXDP) compared to controls, but increased in the cerebellum of both male patients and female carriers. Conclusions: Our findings suggest a potential compensatory mechanism in the cerebellum of female carriers regardless of sex. Our study highlights alterations in HEP levels in PwXDP patients and female carriers. [ABSTRACT FROM AUTHOR]

Nonmelanoma skin cancers remain the most widely diagnosed types of cancers globally. Thus, for optimal patient management, it has become imperative that we focus our efforts on the detection and monitoring of cutaneous field carcinogenesis. The concept of field cancerization (or field carcinogenesis), introduced by Slaughter in 1953 in the context of oral cancer, suggests that invasive cancer may emerge from a molecularly and genetically altered field affecting a substantial area of underlying tissue including the skin. A carcinogenic field alteration, present in precancerous tissue over a relatively large area, is not easily detected by routine visualization. Conventional dermoscopy and microscopy imaging are often limited in assessing the entire carcinogenic landscape. Recent efforts have suggested the use of noninvasive mesoscopic (between microscopic and macroscopic) optical imaging methods that can detect chronic inflammatory features to identify pre‐cancerous and cancerous angiogenic changes in tissue microenvironments. This concise review covers major types of mesoscopic optical imaging modalities capable of assessing pro‐inflammatory cues by quantifying blood haemoglobin parameters and hemodynamics. Importantly, these imaging modalities demonstrate the ability to detect angiogenesis and inflammation associated with actinically damaged skin. Representative experimental preclinical and human clinical studies using these imaging methods provide biological and clinical relevance to cutaneous field carcinogenesis in altered tissue microenvironments in the apparently normal epidermis and dermis. Overall, mesoscopic optical imaging modalities assessing chronic inflammatory hyperemia can enhance the understanding of cutaneous field carcinogenesis, offer a window of intervention and monitoring for actinic keratoses and nonmelanoma skin cancers and maximise currently available treatment options. [ABSTRACT FROM AUTHOR]

Introduction. The impact of renal allograft rejection treatment on infection development has not been formally defined in the literature. Methods. We conducted a retrospective cohort study of 185 rejection (case) and 185 nonrejection (control) kidney transplant patients treated at our institution from 2014 to 2020 to understand the impact of rejection on infection development. Propensity scoring was used to match cohorts. We collected data for infections within 6 months of rejection for the cases and 18 months posttransplant for controls. Results. In 370 patients, we identified 466 infections, 297 in the controls, and 169 in the cases. Urinary tract infections (38.9%) and cytomegalovirus viremia (13.7%) were most common. Cumulative incidence of infection between the case and controls was 2.17 (CI 1.54–3.05); p < 0.001. There was no difference in overall survival (HR 0.90, CI 0.49–1.66) or graft survival (HR 1.27, CI 0.74–2.20) between the groups. There was a significant difference in overall survival (HR 2.28, CI 1.14–4.55; p = 0.019) and graft survival (HR 1.98, CI 1.10–3.56; p = 0.023) when patients with infection were compared to those without. Conclusions. As previously understood, rejection treatment is a risk factor for subsequent infection development. Our data have defined this relationship more clearly. This study is unique, however, in that we found that infections, but not rejection, negatively impacted both overall patient survival and allograft survival, likely due to our institution's robust post-rejection protocols. Clinicians should monitor patients closely for infections in the post-rejection period and have a low threshold to treat these infections while also restarting appropriate prophylaxis. [ABSTRACT FROM AUTHOR]

Objective: Opportunities exist to improve intraoperative communication and documentation of resection margin details. We instituted a "frozen section timeout" that centers around visualization of the paired resection specimen and surgical defect—facilitating effective, bidirectional exchange of information. Methods: We designed an interactive form for use during the "frozen section timeout" including annotated 3D virtual models of the resected specimen and surgical defect, plus a "line‐item" table for primary and supplemental margin results. The "timeout" was conducted over a Zoom call between the operating room and frozen section laboratory. The form was simultaneously projected and discussed while all members of the surgical care team stopped activities. Nurses, co‐surgeons, and all other members of the surgical team were encouraged to take part in this process. Results: Twenty‐six frozen section timeouts were conducted during head and neck surgeries in the Department of Otolaryngology at Mount Sinai West Hospital. These timeouts were facilitated by the lead surgeon, and all other activities were halted to ensure that critical information was shared, documented, and agreed upon. During the timeout, the annotated specimen and defect scans were displayed, clearly demonstrating the at‐risk margins and the corresponding location and breadth of supplemental margins harvested. Conclusion: Incorporating a frozen section timeout can improve intraoperative communication, increase transparency, and potentially eliminate uncertainty regarding margin status and tumor clearance. Visualization of at‐risk margins and the corresponding location and breadth of supplemental margins promises an unprecedented level of documentation and understanding. This novel technique can establish a new and improved standard of care. Level of Evidence: NA Laryngoscope, 134:725–731, 2024 [ABSTRACT FROM AUTHOR]

Although rare, pulmonary arterial hypertension (PAH) is associated with substantial morbidity and a median survival of approximately 7 years, even with treatment. Current medical therapies have a primarily vasodilatory effect and do not modify the underlying pathology of the disease. CS1 is a novel oral, controlled‐release formulation of valproic acid, which exhibits a multi‐targeted mode of action (pulmonary pressure reduction, reversal of vascular remodeling, anti‐inflammatory, anti‐fibrotic, and anti‐thrombotic) and therefore potential for disease modification and right ventricular modeling in patients with PAH. A Phase 1 study conducted in healthy volunteers indicated favorable safety and tolerability, with no increased risk of bleeding and significant reduction of plasminogen activator inhibitor 1. In an ongoing randomized Phase 2 clinical trial, three doses of open‐label CS1 administered for 12 weeks is evaluating the use of multiple outcome measures. The primary endpoint is safety and tolerability, as measured by the occurrence of adverse events. Secondary outcome measures include the use of the CardioMEMS™ HF System, which provides a noninvasive method of monitoring pulmonary artery pressure, as well as cardiac magnetic resonance imaging and echocardiography. Other outcomes include changes in risk stratification (using the REVEAL 2.0 and REVEAL Lite 2 tools), patient reported outcomes, functional capacity, 6‐min walk distance, actigraphy, and biomarkers. The pharmacokinetic profile of CS1 will also be evaluated. Overall, the novel design and unique, extensive clinical phenotyping of participants in this trial will provide ample evidence to inform the design of any future Phase 3 studies with CS1. [ABSTRACT FROM AUTHOR]

Objective: Division of the sternothyroid muscle during thyroidectomy is a widely accepted surgical technique to provide improved exposure of the thyroid gland, thus facilitating the ligation of superior pole vessels and identification of the laryngeal nerves. However, few have examined the impact on voice outcomes. We evaluate the impact of sternothyroid muscle division on patient‐perceived voice outcomes after thyroidectomy. Study Design: Prospective cohort study. Setting: Tertiary academic institution. Methods: A prospective cohort study was conducted comparing pre‐ and postoperative voice outcome data after thyroidectomy, measured using Voice Handicap Index‐10. The cohort of 109 patients underwent lobectomy or total thyroidectomy by a single surgeon at 1 institution. The sternothyroid muscle was fully divided in all surgeries. The integrity of the recurrent laryngeal and external branches of the superior laryngeal nerve was assessed using intraoperative nerve monitoring and postoperative laryngoscopy. Pre‐ and postoperative Voice Handicap Index‐10 scores were compared. Results: No statistically significant difference was found between total pre‐ and postoperative Voice Handicap Index‐10 scores (μpreop = 1.92, μpostop = 1.83, p =.87). There were no questions yielding statistically significant responses between pre‐ and postoperative groups. This was consistent regardless of whether the sternothyroid muscle was cut unilaterally or bilaterally. Men showed a statistically significant improvement in score after surgery. Conclusion: These findings support no difference in postoperative voice outcomes after the intraoperative division of the sternothyroid muscle. This supports the usage of this technique as a safe means to facilitate exposure during thyroid surgery and will serve as important information to guide intraoperative surgical decision‐making. [ABSTRACT FROM AUTHOR]

Background: Urinary Tract Infections are the most common post‐transplant infection and can have varied presentations. This study aimed to describe the outcomes of kidney transplant recipients with asymptomatic histologic pyelonephritis on allograft biopsy. Histologic Pyelonephritis was defined as neutrophil cast or neutrophilic tubulitis, interstitial infiltrates with predominant neutrophils, and no evidence of rejection or glomerulonephritis on biopsy. Methods: The study included 123 kidney transplant recipients, of whom 95 underwent protocol biopsies, and 28 had biopsies for elevated creatinine within the first 2 years of a kidney transplant. Results: The mean age of the cohort was 55.3 years, with 52% females and 78% deceased donor transplants. The risk factors for asymptomatic histologic pyelonephritis were recipient female sex (OR 1.89, 1.3–2.7, diabetes mellitus (OR 2.479, 1.687–3.645), and deceased donation (OR 1.69, 1.098–2.63). The incidence of asymptomatic pyelonephritis on protocol biopsy was 1.7%, with 52% having positive urine cultures and Escherichia coli being the most common bacteria. Subjects with asymptomatic pyelonephritis had inferior graft survival compared to the matched cohort HR 1.88 (1.06–3.35), p =.0281. In addition, of these 123 subjects, 68 (55%) subsequently developed pyelonephritis, and 34 subjects had pyelonephritis within 6 months after this episode. Subjects with recurrent infections exhibited lower survival HR 2.86 (1.36–6.02) and a trend toward higher rejection risk. Conclusion: Asymptomatic histologic pyelonephritis can occur in kidney transplant recipients and is associated with inferior graft survival. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the long‐term outcomes of Hispanic versus white recipients who underwent simultaneous pancreas kidney transplantation (SPKT). This single‐center study, conducted from 2003 to 2022, had a median follow‐up of 7.5 years. The study included 91 Hispanic and 202 white SPKT recipients. The mean age (44 vs. 46 years), percentage of males (67% vs. 58%), and body mass index (BMI) (25.6 vs. 25.3 kg/m2) were similar between the Hispanic and white groups. The Hispanic group had more recipients with type 2 diabetes (38%) compared to the white group (5%, p <.001). The duration of dialysis was longer in Hispanics (640 vs. 473 days, p =.02), and fewer patients received preemptive transplants (10% vs. 29%, p <.01) compared to whites. Hospital length of stay, rates of BK Viremia, and acute rejection episodes within 1 year were similar between the groups. The estimated 5‐year kidney, pancreas, and patient survival rates were also similar between the groups, 94%, 81%, and 95% in Hispanics, compared to 90%, 79%, and 90% in whites. Increasing age and longer duration of dialysis were risk factors for death. Although Hispanic recipients had a longer duration on dialysis and fewer preemptive transplants, the survival rates were similar to those of white recipients. However, referring providers and many transplant centers continue to overlook pancreas transplants for appropriately selected patients with type 2 diabetes, particularly among minority populations. As a transplant community, it is crucial that we make efforts to comprehend and tackle these obstacles to transplantation. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post‐transplant year with outcomes after kidney transplantation. Methods: We conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post‐transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx‐all GEP results normal, 1 Not‐TX had one GEP result abnormal and >1 Not‐TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation. Results: We enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n = 117 (47%), 1 Not‐TX n = 59 (25%) and >1 Not‐TX n = 64 (27%). Compared to the TX group, the >1 Not‐TX group had lower eGFR (p <.001) and more chronic changes on 1‐year surveillance biopsy (p =.007). Death censored graft survival showed inferior graft survival in the >1 Not‐TX group (p <.001) but not in the 1 Not‐TX group. All graft losses in the >1 Not‐TX group occurred after 1‐year post‐transplant. Conclusions: We conclude that a pattern of persistently Not‐TX GEP assay correlates with inferior graft survival. [ABSTRACT FROM AUTHOR]

Background: Neutrophil‐to‐lymphocyte ratio (NLR) is a biomarker of systemic inflammation that is associated with adverse oncologic and surgical outcomes. We investigated the use of NLR as a prognostic indicator of complications of head and neck cancer (HNC) surgeries. Methods: We conducted a retrospective study of 11 187 Veterans who underwent HNC surgery between 2000 and 2020. We calculated preoperative NLR values and fit logistic regression models adjusting for potential confounding factors, comparing high‐NLR patients to low‐NLR patients. Results: The cohort had a median age of 63 and was 98% men. High‐NLR patients had increased odds of 30‐day mortality (p < 0.001), having 1+ perioperative complications (p < 0.001), sepsis (p = 0.03), failure to wean from mechanical ventilation (p = 0.04), pneumonia (p < 0.001), and pulmonary embolism (p = 0.02) compared with low‐NLR patients. Conclusion: NLR was a robust, independent predictor of 30‐day mortality, having 1+ surgical complications, sepsis, failure to wean from mechanical ventilation, pneumonia, and pulmonary embolism. [ABSTRACT FROM AUTHOR]

This study sought to understand COVID‐19‐related organizational decisions were made across sectors. To gain this understanding, we conducted semi‐structured interviews with organizational decision‐makers in North Carolina about their experiences responding to COVID‐19. Conventional content analysis was used to analyse the context, inputs, and processes involved in decision‐making. Between October 2020 and February 2021, we interviewed 44 decision‐makers from the following sectors: business (n = 4), community non‐profit (n = 3), county government (n = 4), healthcare (n = 5), local public health (n = 5), public safety (n = 7), religious (n = 6), education (n = 7) and transportation (n = 3). We found that during the pandemic, organizations looked to scientific authorities, the decisions of peer organizations, data about COVID‐19, and their own experience with prior crises. Interpretation of inputs was informed by current political events, societal trends, and organization mission. Decision‐makers had to account for divergent internal opinions and community behaviour. To navigate inputs and contextual factors, organizations decentralized decision‐making authority, formed auxiliary decision‐making bodies, learned to resolve internal conflicts, learned in real time from their crisis response, and routinely communicated decisions with their communities. In conclusion, aligned with systems and contingency theories of decision‐making, decision‐making during COVID‐19 depended on an organization's 'fit' within the specifics of their existing system and their ability to orient the dynamics of that system to their own goals. [ABSTRACT FROM AUTHOR]

In neurodegenerative diseases, the characterization of the prodromal phase is essential for the future application of disease‐modifying therapies. X‐linked dystonia‐parkinsonism is a hereditary neurodegenerative movement disorder characterized by severe adult‐onset dystonia accompanied by parkinsonism. Distinct striatal and pallidal atrophy is present already in early disease stages indicating a long‐lasting presymptomatic degenerative process. To gain insight into the prodromal phase of X‐linked dystonia‐parkinsonism, structural and iron‐sensitive magnetic resonance imaging (MRI) was performed in 10 non‐manifesting carriers and 24 healthy controls in a double‐blind fashion. Seventeen patients with X‐linked dystonia‐parkinsonism were recruited to replicate previous findings of basal ganglia pathology and iron accumulation. Age at onset was estimated in non‐manifesting carriers and patients using the repeat length of the hexanucleotide expansion and 3 single‐nucleotide polymorphisms associated with age at onset. Voxel‐based morphometry and subcortical volumetry showed striatal and pallidal atrophy in non‐manifesting carriers (~10%) and patients (~40%). Substantia nigra volume was similarly reduced in patients (~40%). Caudate volume correlated with time to estimated onset in non‐manifesting carriers. Susceptibility‐weighted imaging confirmed iron deposition in the anteromedial putamen in patients. Non‐manifesting carriers also showed small clusters of iron accumulation in the same area after lowering the statistical threshold. In conclusion, basal ganglia atrophy and iron accumulation precede the clinical onset of X‐linked dystonia‐parkinsonism and can be detected years before the estimated disease manifestation. It thereby highlights the potential of multimodal imaging to identify clinically unaffected mutation carriers with incipient neurodegeneration and to monitor disease progression independent of clinical measures. Longitudinal studies are needed to further elucidate the onset and progression rate of neurodegeneration in prodromal X‐linked dystonia‐parkinsonism. ANN NEUROL 2023;93:999–1011 [ABSTRACT FROM AUTHOR]

Aims: To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults with pulmonary arterial hypertension (PAH). Methods and results: We followed the European Society of Cardiology (ESC) methodology for the development of QIs. This included (i) the identification of key domains of care for the management of PAH, (ii) the proposal of candidate QIs following systematic review of the literature, and (iii) the selection of a set of QIs using a modified Delphi method. The process was undertaken in parallel with the writing of the 2022 ESC/European Respiratory Society (ERS) guidelines for the diagnosis and treatment of pulmonary hypertension and involved the Task Force chairs, experts in PAH, Heart Failure Association (HFA) members and patient representatives. We identified five domains of care for patients with PAH: structural framework, diagnosis and risk stratification, initial treatment, follow‐up, and outcomes. In total, 23 main and one secondary QIs for PAH were selected. Conclusion: This document presents the ESC QIs for PAH, describes their development process and offers scientific rationale for their selection. The indicators may be used to quantify and improve adherence to guideline‐recommended clinical practice and improve patient outcomes. [ABSTRACT FROM AUTHOR]

There is growing interest in a data integration approach to survey sampling, particularly where population registers are linked for sampling and subsequent analysis. The reason for doing this is simple: it is only by linking the same individuals in the different sources that it becomes possible to create a data set suitable for analysis. But data linkage is not error free. Many linkages are nondeterministic, based on how likely a linking decision corresponds to a correct match, that is, it brings together the same individual in all sources. High quality linking will ensure that the probability of this happening is high. Analysis of the linked data should take account of this additional source of error when this is not the case. This is especially true for secondary analysis carried out without access to the linking information, that is, the often confidential data that agencies use in their record matching. We describe an inferential framework that allows for linkage errors when sampling from linked registers. After first reviewing current research activity in this area, we focus on secondary analysis and linear regression modeling, including the important special case of estimation of subpopulation and small area means. In doing so we consider both robustness and efficiency of the resulting linked data inferences. This article is categorized under:Algorithms and Computational Methods > Maximum Likelihood MethodsStatistical Learning and Exploratory Methods of the Data Sciences > Modeling MethodsStatistical and Graphical Methods of Data Analysis > Multivariate Analysis [ABSTRACT FROM AUTHOR]

Background: Evidence exists that escalating melanoma incidence is due in part to overdiagnosis, the diagnosis of lesions that will not lead to symptoms or death. The authors aimed to characterize subsets of melanoma patients with very‐low risk of death that may be contributing to overdiagnosis. Methods: Melanoma patients diagnosed in 2010 and 2011 with stage I lesions ≤1.0 mm thick and negative clinical lymph nodes from the Surveillance, Epidemiology, and End Results database were selected. Classification and regression tree and logistic regression models were developed and validated to identify patients with very‐low risk of death from melanoma within 7 years. Logistic models were also used to identify patients at higher risk of death among this group of stage I patients. Results: Compared to an overall 7‐year mortality from melanoma of 2.5% in these patients, a subset comprising 25% had a risk below 1%. Younger age at diagnosis and Clark level II were associated with low risk of death in all models. Breslow thickness below 0.4 mm, absence of mitogenicity, absence of ulceration, and female sex were also associated with lower mortality. A small subset of high‐risk patients with >20% risk of death was also identified. Conclusion: Patients with very‐low risk of dying from melanoma within 7 years of diagnosis were identified. Such cases warrant further study and consensus discussion to develop classification criteria, with the potential to be categorized using an alternative term such as "melanocytic neoplasms of low malignant potential." Lay summary: Although melanoma is the most serious skin cancer, most melanoma patients have high chances of survival.There is evidence that some lesions diagnosed as melanoma would never have caused symptoms or death, a phenomenon known as overdiagnosis.In this study, we used cancer registry data to identify a subset of early‐stage melanoma patients with almost no melanoma deaths.Using two statistical approaches, we identified patients with <1% risk of dying from melanoma in 7 years.Such patients tended to be younger with minimal invasion into the skin.We also identified a very small patient subset with higher mortality risk. This Surveillance, Epidemiology, and End Results analysis identified subsets of stage I melanoma patients with <1% risk of death from melanoma within 7 years of diagnosis. Clark level II invasion and younger patient age were associated with lower risk of death from melanoma. [ABSTRACT FROM AUTHOR]

Background: The pleiotropic effects of statin therapy on inflammation and coagulation may reduce the risk of venous thromboembolism. This study evaluated whether statin therapy is associated with decreased venous thromboembolic (VTE) events following kidney transplantation. Methods: We performed a retrospective analysis of all primary kidney transplants performed between January 2014 and December 2019 at Mayo Clinic Arizona. Patients were divided into two groups depending on sustained statin therapy during the first year following transplantation. Recipient and donor clinical and demographic data were collected. The primary outcome was admission for symptomatic VTE events (deep vein thrombosis [DVT] or pulmonary embolism [PE]). Results: Sustained statin therapy in the first year following transplant was observed in 16.1% (n = 223) of 1384 kidney transplants. The overall incidence of VTE events in the year following kidney transplant was 3.8%. VTE occurred in 4.1% of recipients treated with statins and 3.8% of the controls – (hazard ratio [HR].92, 95% confidence interval [95% CI].39, 2.21, p =.86). However, there were significant differences between the groups in terms of age, sex, race/ethnicity, body mass index, indication for transplant, diagnosis of diabetes and discharge antiplatelet or anticoagulant therapy. Following sensitivity analysis in which cohort matching was performed to account for these differences, there was no difference in VTE event‐free survival (HR.89, 95% CI.41, 1.96, p =.78) or overall survival (HR.54, 95% CI.15, 1.94, p =.35) between patients treated with statins compared to controls. Conclusion: Statin therapy in the year following successful kidney transplant was not associated with a reduction in risk of VTE. [ABSTRACT FROM AUTHOR]

Introduction: Infections are known complications of solid‐organ transplant. Treatment for rejection may increase risk of infection. We aimed to study frequency of infection and identify the risk factors for infections in solid organ transplant (SOT) (liver and kidney) recipients treated for rejection. Methods: This is a retrospective chart review of all liver and kidney transplant recipients treated for rejection at our institution from 2014 to 2020. We collected information on episodes of acute rejection in the first year of transplant and infections within 6 months following rejection treatment. Results: We identified 257 transplant patients treated for rejection. One hundred twelve (43.6%) developed infections, with a total of 226 infections. Urinary tracts infections were the most common, 72 (31.9%), followed by cytomegalovirus viremia in 37 (16.4%), bacteremia in 24 (10.6%), and BK virus in 14 (6.2%). Female sex (p =.047), elevated neutrophil count at rejection (p =.002), and increased number of rejection episodes (p =.022) were predictors of infection in kidney and simultaneous liver‐kidney recipients. No specific type of induction or rejection therapy was identified as a risk factor for infection, likely due to the prophylaxis protocols at our institution. Infection post rejection treatment was associated with higher graft loss (p =.021) and mortality (p =.031) in kidney transplant recipients. Conclusions: Infections are common complications after treatment of SOT rejection. Female gender, higher neutrophil at time of rejection, and increased numbers of rejection episodes were predictors of infections after rejection in simultaneous liver‐kidney and kidney transplant patients. Infections were predictors of graft loss at 6 months and mortality at any point in follow‐up in kidney transplant patients. [ABSTRACT FROM AUTHOR]

With increasing pressure for climate action, commitments to setting scientifically supported emissions targets have become more common among firms. The target‐setting methods currently endorsed by the Science Based Targets Initiative (SBTi) use emission pathways that are aligned with 1.5°C and well‐below 2°C long‐term temperature goals to inform near‐term corporate targets. However, most of these scenarios lead to a temperature overshoot, followed by a return to the temperature goal achieved via net‐negative emissions in the second half of this century. When used to inform near‐term (e.g., 2030) corporate targets, the result is a set of targets that are aligned with an overshoot of a temperature target, with no explicit long‐term commitment to using negative emissions technologies to reverse this. To decrease the risk of this misalignment with the long‐term temperature goal, we propose an alternative approach that derives corporate targets directly from the remaining global cumulative carbon budget. We illustrate this approach using global Scope 1 emissions disclosed by public firms in 2019 to estimate corporate carbon budgets and construct idealized emissions‐reduction pathways that are consistent with the remaining global carbon budget for 1.5°C and well‐below 2°C. While firms, or their sectors, may choose varying mitigation pathways aligned with either global temperature limit, consistency with remaining carbon budgets requires that any delayed mitigation action in the near term is followed by more rapid emissions reductions in subsequent years. This study emphasizes the need for a more precautionary and robust approach to corporate target setting. [ABSTRACT FROM AUTHOR]

The INSPIRE trial was a Phase 3, open‐label, multicenter trial (LTI‐301) that enrolled patients with pulmonary arterial hypertension (PAH) ≥ 18 years of age who transitioned to Yutrepia from nebulized treprostinil (Transition) or added Yutrepia to prostacyclin naïve patients on ≤2 nonprostacyclin oral therapies. The objectives of the trial were to evaluate the safety and tolerability of Yutrepia (dry‐powder formulation of treprostinil) in patients with PAH. The primary safety measures were the incidence of adverse events (AEs) and serious AEs. Exploratory efficacy measures were also assessed during the trial. Transition patients initiated Yutrepia at a dose comparable to their nebulized treprostinil dose while prostacyclin naïve patients received 26.5‐mcg QID; up‐titration in 26.5‐mcg increments was permitted for both groups. A total of 121 patients were enrolled, of which 29 patients discontinued from the trial, with the most common reason being AEs. Eighty percent of the Transition group and 96% of the prostacyclin naïve group titrated to a dose ≥79.5 mcg QID at Day 360, respectively, with one patient achieving a dose of 212‐mcg QID. The most common AEs were cough, headache, upper respiratory tract infection, dyspnea, dizziness, throat irritation, diarrhea, chest discomfort, fatigue, and nasopharyngitis. Most of these events were considered treatment‐related though mild to moderate in severity and expected for prostacyclin therapy administered by inhalation. In an evaluation of exploratory efficacy measures, patients remained stable or improved over the 1 year of treatment. Yutrepia was found to be a convenient, safe, and well‐tolerated inhaled prostacyclin treatment option for PAH patients. [ABSTRACT FROM AUTHOR]

Background: Centers discard high kidney donor profile index (KDPI) allografts, potentially related to delayed graft function and prolonged hospital use by kidney transplant recipients (KTR). We sought to determine whether high KDPI KTRs have excess health care utilization. Methods: We conducted a retrospective cohort study from a high‐volume center analyzing KTRs from January 3, 2011 to April 12, 2015 (n = 652). We measured differences in hospital use, emergency visits, and outpatient visits within the first 90 days between low (≤85%) versus high KDPI (>85%) KTRs, as well as long‐term graft function and patient survival. Results: High (n = 107) and low KDPI (n = 545) KTRs had similar length of stay (median = 3 days, P =.66), and readmission rates at 7, 30, and 90 days after surgery (all, P >.05). High KDPI kidneys were not associated with excess utilization of the hospital, emergency services, outpatient transplant clinics, or ambulatory infusion visits on univariate or multivariate analysis (all, P >.05). Low KDPI KTRs had significantly better eGFR at 2 years (Low vs. High KDPI: 60.35 vs. 41.54 ml/min, P <.001), but similar 3‐year patient and graft survival (both, P >.09). Conclusions: High and low KDPI KTRs demonstrated similar 90‐day risk‐adjusted health care utilization, which should encourage use of high KDPI kidneys. [ABSTRACT FROM AUTHOR]

The purpose of this study is to characterize the population pharmacokinetics (popPK) of subcutaneous (SC) daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone and explore the relationship between daratumumab systemic exposure and selected efficacy and safety end points in patients with newly diagnosed systemic amyloid light‐chain amyloidosis. The popPK analysis included pharmacokinetic and immunogenicity data from patients receiving daratumumab SC in combination with bortezomib, cyclophosphamide, and dexamethasone in the ANDROMEDA study (AMY3001; safety run‐in, n = 28; randomized phase, n = 183). Nonlinear mixed‐effects modeling was used to characterize the popPK and quantify the impact of potential covariates. The exposure‐response (E‐R) analysis included data from all patients in the randomized phase of ANDROMEDA (n = 388). Logistic regression and survival analysis were used to evaluate the relationships between daratumumab systemic exposure and efficacy end points. The E‐R analysis on safety was conducted using quartile comparison and logistic regression analysis. The observed concentration‐time data of daratumumab SC were well described by a 1‐compartment popPK model with first‐order absorption and parallel linear and nonlinear Michaelis‐Menten elimination pathways. None of the investigated covariates were determined to be clinically meaningful. Daratumumab systemic exposure was generally similar across subgroups that achieved different levels of hematologic response, and there was no apparent relationship between daratumumab systemic exposure and the investigated safety end points. In conclusion, the popPK and E‐R analyses supported the selected 1800‐mg flat dose of daratumumab SC in combination with the bortezomib, cyclophosphamide, and dexamethasone regimen for the treatment of light‐chain amyloidosis. No dose adjustment was recommended for investigated covariates. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of DPP-4 inhibition with sitagliptin in youth with type 2 diabetes (T2D). Study Design: This was a 54-week, double-blind, randomized, controlled clinical trial evaluating the safety and efficacy of DPP-4 inhibition with sitagliptin 100 mg once daily as initial oral therapy in youth with T2D. The 190 participants, aged 10--17 years, had HbA1c 6.5%--10% (7.0%--10% if on insulin). All were negative for pancreatic autoantibodies and overweight/obese at screening or diagnosis. The trial was placebo controlled for the first 20 weeks, after which metformin replaced placebo. The primary efficacy endpoint was change from baseline in HbA1c at Week 20. Results: Treatment groups were well balanced at baseline (mean ± SD HbA1c = 7.5% ± 1.0, BMI percentile = 97.1% ± 6.8, age = 14.0 years ± 2.0 [57.4% <15], 60.5% female). At Week 20, least squares mean changes from baseline in HbA1c were -0.01% (sitagliptin) and 0.18% (placebo); between-group difference (95% CI) = -0.19% (-0.68, 0.30), p = 0.448. At Week 54, the changes in HbA1c were 0.45% (sitagliptin) and -0.11 (placebo/metformin). There were no notable between-group differences in the adverse event profiles through Week 54. Conclusions: DPP-4 inhibition with sitagliptin did not provide significant improvement in glycemic control. In this study, sitagliptin was generally well tolerated with a safety profile similar to that reported in adults. (ClinicalTrials.gov: NCT01485614; EudraCT: 2011-002528-42) [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of sitagliptin in youth with type 2 diabetes (T2D) inadequately controlled with metformin ± insulin. Study Design: Data were pooled from two 54-week, double-blind, randomized, placebo-controlled studies of sitagliptin 100 mg daily or placebo added onto treatment of 10- to 17-year-old youth with T2D and inadequate glycemic control on metformin ± insulin. Participants (N = 220 randomized and treated) had HbA1c 6.5%--10% (7.0%--10% if on insulin), were overweight/obese at screening or diagnosis and negative for pancreatic autoantibodies. The primary endpoint was change from baseline in HbA1c at Week 20. Results: Treatment groups were well balanced at baseline (mean HbA1c = 8.0%, BMI = 30.9 kg/m², age = 14.4 years [44.5% <15], 65.9% female). The dose of background metformin was >1500 mg/day for 71.8% of participants; 15.0% of participants were on insulin therapy. At Week 20, LS mean changes from baseline (95% CI) in HbA1c for sitagliptin/metformin and placebo/metformin were -0.58% (-0.94, -0.22) and -0.09% (-0.43, 0.26), respectively; difference = -0.49% (-0.90, -0.09), p = 0.018; at Week 54 the LS mean (95% CI) changes were 0.35% (-0.48, 1.19) and 0.73% (-0.08, 1.54), respectively. No meaningful differences between the adverse event profiles of the treatment groups emerged through Week 54. Conclusions: These results do not suggest that addition of sitagliptin to metformin provides durable improvement in glycemic control in youth with T2D. In this study, sitagliptin was generally well tolerated with a safety profile similar to that reported in adults. (ClinicalTrials.gov: NCT01472367, NCT01760447; EudraCT: 2011-002529-23/2014-003583-20, 2012-004035-23). [ABSTRACT FROM AUTHOR]

This study examined associations between structural racism, anti‐LGBTQ policies, and suicide risk among young sexual minority men (SMM). Participants were a 2017–2018 Internet‐based U.S. national sample of 497 Black and 1536 White SMM (ages 16–25). Structural equation modeling tested associations from indicators of structural racism, anti‐LGBTQ policies, and their interaction to suicide risk factors. For Black participants, structural racism and anti‐LGBTQ policies were significantly positively associated with depressive symptoms, heavy drinking, perceived burdensomeness, thwarted belongingness, self‐harm, and suicide attempt. There were significant interaction effects: Positive associations between structural racism and several outcomes were stronger for Black participants in high anti‐LGBTQ policy states. Structural racism, anti‐LGBTQ policies, and their interaction were not significantly associated with suicide risk for White SMM. [ABSTRACT FROM AUTHOR]

Alpha taxonomy of caddisflies (order Trichoptera) is based primarily on male genital morphology. As such, associations of adult females and other life stages typically require conclusive association with the species' identifiable male. The aim of this study was to use molecular methods to associate females and larvae of Polycentropus species represented in the Nearctic. Analysis of mtCOI sequences using distance‐ and tree‐based methods resulted in the association of larvae for 14 species of Polycentropus (P. alabamensis Hamilton, Harris & Lago, 1990, P. blicklei Ross & Yamamoto 1965, P. carlsoni Morse 1971, P. carolinensis Banks 1905, P. colei Ross 1941, P. confusus Hagen 1861, P. denningi Smith 1962, P. elarus Ross 1944, P. gertschi Denning 1950, Polycentropus halidus Milne 1936, P. maculatus Banks 1908, P. pentus Ross 1941, P. rickeri Yamamoto 1966, and P. variegatus Banks 1900) and females for 2 species (P. carolinensis and P. chelatus Ross & Yamamoto 1965). Searches for, and descriptions of, diagnostic morphological characters for these previously unidentifiable life forms are now possible. The identity of the larva of P. centralis Banks, 1914 is confirmed and some interesting phylogenetic relationships and a possible cryptic species and potential synonyms are implied in the results. Targets for future immature‐ and female–male associations are discussed along with a preliminary assessment of morphological differences among larvae. [ABSTRACT FROM AUTHOR]

Background: Histopathologically ambiguous melanocytic lesions lead some pathologists to list multiple diagnostic considerations in the pathology report. The frequency and circumstance of multiple diagnostic considerations remain poorly characterized. Methods: Two hundred and forty skin biopsy samples were interpreted by 187 pathologists (8976 independent diagnoses) and classified according to a diagnostic/treatment stratification (MPATH‐Dx). Results: Multiple diagnoses in different MPATH‐Dx classes were used in n = 1320 (14.7%) interpretations, with 97% of pathologists and 91% of cases having at least one such interpretation. Multiple diagnoses were more common for intermediate risk lesions and are associated with greater subjective difficulty and lower confidence. We estimate that 6% of pathology reports for melanocytic lesions in the United States contain two diagnoses of different MPATH‐Dx prognostic classes, and 2% of cases are given two diagnoses with significant treatment implications. Conclusions: Difficult melanocytic diagnoses in skin may necessitate multiple diagnostic considerations; however, as patients increasingly access their health records and retrieve pathology reports (as mandated by US law), uncertainty should be expressed unambiguously. [ABSTRACT FROM AUTHOR]

Objective: To measure the effect of thyroidectomy difficulty on intraoperative neuromonitoring false loss of signal (LOS) and to compare intraoperative endotracheal tube–based neuromonitoring (ETNM) and Checkpoint palpation-based direct stimulation (pDS) signals with postoperative laryngoscopy. We hypothesized that pDS has higher a positive predictive value for postdissection confirmation of recurrent laryngeal nerve function than ETNM and that this difference is accentuated with increasing thyroidectomy difficulty. Study Design: Prospective single-arm cross-sectional study comparing ETNM and pDS for patients undergoing hemi-, total, or completion thyroidectomy from July 2018 to March 2020. Setting: Single-surgeon series at a tertiary care hospital. Methods: Percentage concordance and positive and negative predictive values were measured. Each thyroidectomy was assigned a validated thyroidectomy difficulty score, and recorded recurrent laryngeal nerve signals were compared with postoperative vocal fold mobility. Results: Percentage concordance was 90.09%. Positive and negative predictive values were 0.19 (95% CI, 0.09-0.31) and 1.0 for ETNM and 0.59 (95% CI, 0.35-0.82) and 1.0 for pDS. The difference in positive predictive value was significant (0.40 [95% CI, 0.33-0.47], P <.001). False LOS rates for ETNM and pDS were 13.19% versus 3.30% (9.89% [95% CI, 1.80%-18.62%], P =.0155), 44.11% versus 0% (44.11% [95% CI, 25.80%-60.54%], P <.001), and 73.33% versus 13.33% (60% [95% CI, 24.76%-78.46%], P =.001) for the second through fourth thyroidectomy difficulty score quartiles, respectively. False LOS with ETNM was linearly correlated with increasing difficulty (R 2 = 0.97). Conclusion: ETNM was subject to high rates of postdissection false LOS that increased with thyroidectomy difficulty score. pDS is a reliable alternative that has higher positive predictive value than ETNM, particularly in more challenging cases such as those with posteriorly fixed thyroid cancers and fibrotic glands. Evidence level: 2. [ABSTRACT FROM AUTHOR]

Background and objectives: We aimed to determine outcomes with transplanting kidneys from deceased donors with severe acute kidney injury requiring acute renal replacement therapy (RRT). Materials and methods: A total of 172 recipients received a kidney from donors with acute kidney injury stage 3 (AKIN3) requiring RRT. We compared the study group to 528 recipients who received a kidney from donors with AKIN stage 3 not on RRT and 463 recipients who received < 85% Kidney Donor Profile Index (KDPI) AKIN stage 0 kidney. Results: The study group donors were younger compared to the 2 control groups. Despite higher DGF in the study group, the length of hospital stay and acute rejection were similar. Death censored graft survival (96% AKIN3‐RRT vs. 97%AKIN3 no RRT vs. 96% KDPI < 85% AKIN0, P = 0.26) and patient survival with functioning graft at 1 year (95% across all groups, P = 0.402) were similar. The estimated glomerular filtration rate were similar across the 3 groups after first month. Interstitial fibrosis and tubular atrophy score ≥ 2 on protocol biopsy at time 0, 4 and 12 months were similar. Primary nonfunction was rare and associated with high KDPI. Conclusions: Transplanting selected kidneys from deceased donors with AKIN3 requiring RRT is safe and has good outcomes. [ABSTRACT FROM AUTHOR]

Recent advances in retinal imaging technology have improved our understanding in the pathogenesis and evolvement of various chorioretinal diseases. Central serous chorioretinopathy and polypoidal choroidal vasculopathy are now recognized to belong to the same spectrum of disorders known as pachychoroid diseases. Pachychoroid diseases have similar pathogenesis pathway and common characteristics of thickened choroid, dilated outer choroidal vessels, and thinning of choriocapillaris. More disease entities have been identified to belong to this disease spectrum. Photodynamic therapy can induce choroidal hypoperfusion, remodeling of abnormal choroidal vessels, and reduction of choroidal congestion. It is known to be an effective treatment for chronic central serous chorioretinopathy and polypoidal choroidal vasculopathy. Many new studies are being performed to investigate its efficacy in other pachychoroid diseases. In this review, we provided an overview of the rationale, efficacy, and treatment strategies of photodynamic therapy in different pachychoroid diseases and discussed its role in the management along with other treatment modalities with most updated clinical evidence. [ABSTRACT FROM AUTHOR]

Background: Synoptic reporting is recommended by many guideline committees to encourage the thorough histologic documentation necessary for optimal management of patients with melanoma. Methods: One hundred fifty‐one pathologists from 40 US states interpreted 41 invasive melanoma cases. For each synoptic reporting factor, the authors identified cases with "complete agreement" (all participants recorded the same value) versus any disagreement. Pairwise agreement was calculated for each case as the proportion of pairs of responses that agreed, where paired responses were generated by the comparison of each reviewer's response with all others. Results: There was complete agreement among all reviewers for 22 of the 41 cases (54%) on Breslow thickness dichotomized at 0.8 mm, with pairwise agreement ranging from 49% to 100% across the 41 cases. There was complete agreement for "no ulceration" in 24 of the 41 cases (59%), with pairwise agreement ranging from 42% to 100%. Tumor transected at base had complete agreement for 26 of the 41 cases (63%), with pairwise agreement ranging from 31% to 100%. Mitotic rate, categorized as 0/mm2, 1/mm2, or 2/mm2, had complete agreement for 17 of the 41 cases (41%), with pairwise agreement ranging from 36% to 100%. Regression saw complete agreement for 14 of 41 cases (34%), with pairwise agreement ranging from 40% to 100%. Lymphovascular invasion, perineural invasion, and microscopic satellites were rarely reported as present. Respectively, these prognostic factors had complete agreement for 32 (78%), 37 (90%), and 18 (44%) of the 41 cases, and the ranges of pairwise agreement were 47% to 100%, 70% to 100%, and 53% to 100%, respectively. Conclusions: These findings alert pathologists and clinicians to the problem of interobserver variability in recording critical prognostic factors. Lay Summary: This study addresses variability in the assessment and reporting of critical characteristics of invasive melanomas that are used by clinicians to guide patient care.The authors characterize the diagnostic variability among pathologists and their reporting methods in light of recently updated national guidelines. Results demonstrate considerable variability in the diagnostic reporting of melanoma with regard to the following: Breslow thickness, mitotic rate, ulceration, regression, and microscopic satellites.This work serves to alert pathologists and clinicians to the existence of variability in reporting these prognostic factors. This work serves to alert pathologists and clinicians alike to an existing problem of interobserver variability in reporting critical histopathological prognostic factors, including Breslow thickness, ulceration, and others, that are requisite to the optimal management of patients with melanoma. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether renal transplant diagnoses substantially change when 2 biopsy sites are chosen and whether contrast‐enhanced ultrasound (CEUS) has value for targeting the second site. Methods: We prospectively enrolled 40 patients undergoing ultrasound‐guided renal transplant biopsy within 2 years of transplant: 20, surveillance; and 20, for cause. A CEUS examination was performed to identify cortical regions with subjectively altered flow. One biopsy was performed at the operator‐preferred (primary) site regardless of CEUS findings. Another biopsy was done at a second location, either targeted to an area in which CEUS perfusion findings differed from the primary site (targeted) or at a random location (secondary) if no other area differed. Specimens were randomly labeled A or B; pathologists were blinded to the CEUS result and biopsy location. Location‐specific CEUS assessments were recorded. Pathologic results were compared, including acute and chronic Banff scores and any new findings from the targeted or secondary biopsy. Results: Forty patients were enrolled between January 2016 and December 2018. No location‐specific pathologic differences correlated with differences in CEUS assessments. The second biopsy provided additional information that changed management in 4 of 40 patients (10.0% [95% confidence interval, 2.8%–23.7%]). Major bleeding complications occurred in 3 of 40 (7.5%) patients. Conclusions: Contrast‐enhanced ultrasound targeting was not useful. Major bleeding complications were higher than expected, possibly due to the additional biopsy away from the operator‐preferred location. Obtaining a second renal transplant biopsy from a substantially different area than the initial operator‐preferred location provided additional clinically useful information in 10% of patients. Access the CME test here and search by article title. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: The primary objective of this study was to assess the safety of parathyroidectomy during pregnancy as treatment for hyperparathyroidism (HPTH) in comparison to nonsurgical management plans. Secondary outcomes involved analyzing the safety of surgery in the third trimester and the benefit of operating on asymptomatic pregnant patients. Study Design: Systematic review. Methods: PRISMA‐guided systematic review of all cases of primary hyperparathyroidism during pregnancy published in peer‐reviewed English journals on PubMed/MEDLINE, EMBASE, and SCOPUS from 1980 to 2020. Results: A total of 75 manuscripts were included in this review describing 382 cases of gestational hyperparathyroidism. The median maternal age was 31 years. Overall, 108 cases (28.3%) underwent parathyroidectomy during pregnancy while 274 cases (71.7%) were treated nonsurgically. The majority of surgeries took place during the second trimester (67.6%). Complications and/or deaths were less likely to occur after surgery in the second trimester (4.48%) as compared to surgery in the third trimester (21.1%). Nine surgically treated cases resulted in infant complications and/or death; however, none of these nine cases had any surgical complications. Despite these complications, the overall infant complication rate for patients who underwent surgical treatment remained lower than that of patients treated with conservative therapy (9.1% vs. 38.9%). Conclusions: This review suggests that for all pregnant patients with diagnosed HPTH, parathyroidectomy should be considered regardless of symptomatology. Our data suggest that parathyroidectomy is associated with fewer risks than more conservative treatments and results in better fetal outcomes. Surgery during the third trimester is feasible and surgery should be considered in both symptomatic and asymptomatic patients. Laryngoscope, 131:1915–1921, 2021 [ABSTRACT FROM AUTHOR]

Background: Diagnostic terms used in histopathology reports of cutaneous melanocytic lesions are not standardized. We describe dermatopathologists' views regarding diverse diagnostic terminology and the utility of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH‐Dx) for categorizing melanocytic lesions. Methods: July 2018‐2019 survey of board‐certified and/or fellowship‐trained dermatopathologists with experience interpreting melanocytic lesions. Results: Among 160 participants, 99% reported witnessing different terminology being used for the same melanocytic lesion. Most viewed diverse terminology as confusing to primary care physicians (98%), frustrating to pathologists (83%), requiring more of their time as a consultant (64%), and providing necessary clinical information (52%). Most perceived that adoption of the MPATH‐Dx would: improve communication with other pathologists and treating physicians (87%), generally be a change for the better (80%), improve patient care (79%), be acceptable to clinical colleagues (68%), save time in pathology report documentation (53%), and protect from malpractice (51%). Conclusions: Most dermatopathologists view diverse terminology as contributing to miscommunication with clinicians and patients, adversely impacting patient care. They view the MPATH‐Dx as a promising tool to standardize terminology and improve communication. The MPATH‐Dx may be a useful supplement to conventional pathology reports. Further revision and refinement are necessary for widespread clinical use. [ABSTRACT FROM AUTHOR]