Citations

ImportanceAsymmetric oropharynx uptake on positron emission tomography (PET)/computed tomography (CT) is a common incidental finding and often prompts otolaryngology referral to rule out malignancy; however, the true risk of malignancy based on this finding is unknown.ObjectiveTo identify the incidence of oropharynx cancer in patients with incidental asymmetric oropharynx PET uptake.Design, Setting, and ParticipantsIn this retrospective cohort study, patients 18 years and older undergoing PET/CT scans at Mayo Clinic between January 2001 and December 2018 were included. Patients with a history or pretest suspicion of oropharynx cancer were excluded. Data were analyzed from March 2021 to December 2023.ExposureBlinded radiologic review of imaging studies, including measurement of maximum standardized uptake values (SUVmax) of the ipsilateral side of concern and contralateral side. Retrospective medical record review for associated clinical data.Main Outcomes and MeasuresThe primary study outcome was the incidence of oropharynx cancer diagnosis in patients with asymmetric oropharynx PET uptake. The primary outcome was formulated before data collection.ResultsOf the 1854 patients identified with asymmetric oropharynx PET uptake, 327 (17.6%) met inclusion criteria. Of these, 173 (52.9%) were male, and the median (range) age was 65.0 (24.8-90.7) years. The mean (SD) follow-up interval was 52.1 (43.4) months. A total of 18 of 327 patients (5.5%) were newly diagnosed with oropharynx cancer. The most common diagnosis was squamous cell carcinoma (n = 9), followed by lymphoma (n = 8), and sarcoma (n = 1). Patients with an incidental diagnosis of oropharynx cancer had higher mean (SD) ipsilateral SUVmax (8.7 [3.7] vs 5.3 [1.9]) and SUVmax ratio (3.0 [1.6] vs 1.6 [0.6]) compared with patients with normal examination findings. SUVmax ratio and difference were found to be good discriminators of oropharynx cancer, with areas under the receiver operating characteristic curve of 86.3% (95% CI, 76.4-94.6) and 85.8% (95% CI, 74.8-94.6), respectively. Patients with a new diagnosis of oropharynx cancer were more likely to have a corresponding CT abnormality than those with normal examination findings (6 of 18 [33%] vs 24 of 295 [8.1%]). Patients with concerning lesions on oropharynx palpation by an otolaryngology health care professional were significantly more likely to be diagnosed with oropharynx cancer compared with patients with normal examination findings (odds ratio, 28.4; 95% CI, 6.6-145.8).Conclusions and RelevanceIn this cohort study, while incidental asymmetric oropharynx PET uptake was common, a new diagnosis of oropharynx cancer was not and potentially results in a large volume of unnecessary referrals and work-up. Using SUVmax ratio, SUVmax difference, and CT correlation may increase the benefit of referral. Patients with a palpable oropharynx lesion and asymmetric oropharynx PET uptake should undergo confirmatory biopsy.

AbstractRenal AL amyloidosis can be complicated by end‐stage renal disease (ESRD) requiring renal replacement therapy (RRT). In this study, we describe the long‐term outcomes of renal AL amyloidosis patients undergoing autologous stem cell transplantation (ASCT) and assess the utility of the renal staging system. Retrospective study of renal AL patients (n = 697; Mayo Clinic, Boston University) who underwent ASCT between 2003 and 2020. Renal stage was assigned based on 24‐h proteinuria and estimated glomerular filtration rate measurements. Renal survival was defined as the time from ASCT until initiation of RRT, while patients who were not placed on RRT were censored at their last follow‐up. With a median follow‐up of 10.4 years, RRT was required in 149 patients (21%). The median time from ASCT to ESRD was 3.4 years, with late events of progression to ESRD seen >10 years from ASCT. Pre‐ASCT renal stage was significantly associated with the cumulative incidence of RRT: 3‐year RRT rate was 3%, 10%, and 37% for renal stages I, II, and III, respectively. However, in the 2012–2020 period subset, a significant decrease in ESRD risk was noted across all renal stages (3‐year RRT 0%, 5%, and 24%, respectively). In multivariate analysis, renal survival was independently associated with the pre‐ASCT renal stage, lambda isotype, bone marrow plasmacytosis ≥20%, post‐ASCT hematologic response, and year of ASCT. Long‐term outcomes of renal AL amyloidosis treated with ASCT are presented. Renal stage reliably predicts renal outcomes in patients with AL undergoing ASCT, despite a reduction in the proportion of patients progressing to RRT in recent years.

Abstract Background New immunoglobulin free light chain (FLC) assays are available. Despite analytical differences, it seems possible to use free light chain ratios (FLCr) generated by different assays and apply similar cut-points for the diagnosis of multiple myeloma. It is still unknown if we can use different assays for risk stratification of patients with monoclonal gammopathy of undetermined significance (MGUS). Methods Patients diagnosed with MGUS (N = 923) had FLC tested using a nephelometric FreeLite (Binding Site) assay on BNII instruments (Siemens) and a Sebia FLC assay (Sebia) on a DS2 ELISA analyzer (Dynex). Patients were followed up for progression to any plasma cell dyscrasia (PCD) for several decades. The Mayo MGUS risk stratification model for progression was assessed with both assays (M-spike >1.5 g/dL; non-IgG isotype and abnormal FLCr), using package insert reference intervals (RI) and a new metric called principal component 2 (PC2). Results There were 94 events of progression to PCD in the cohort during a median of 38 years of follow-up. Freelite and Sebia FLC showed similar hazard ratios in the risk models for elevated FLCr. An alternative clinical decision point lower than the package insert RI was evaluated for the Sebia assay, which improved risk stratification for patients with a low FLCr. The PC2 metric showed similar performance to the FLCr in models, without superior benefit. Conclusions The Sebia ELISA-based FLC assay can be employed in an MGUS risk stratification model with similar performance to the original 2005 risk stratification model using the FreeLite assay.

Abstract Background Sphingolipids play a crucial role in cellular functions and are essential components of cell membranes, signaling molecules, and lipid metabolism. In particular, ceramide is a key intermediate in sphingolipid metabolism and defects in ceramide metabolism can lead to various inborn errors of metabolism, making ceramides important targets for clinical screening and diagnosis. Detecting altered concentration patterns of sphingolipids is desirable for distinguishing related inborn errors of metabolism for diagnosis and treatment monitoring. Methods We developed a liquid chromatography-tandem mass spectrometry method with a pathway-oriented approach to focus on sphingolipids involved in ceramide metabolism. A total of 47 sphingolipids bearing different head groups and side chains were targeted. Precision/reproducibility, linearity, and spike recovery extraction efficiency tests were performed on plasma and serum samples from confirmed cases of sphingolipidosis. Results Linearity of the method showed the coefficient of determination (r2) for all standards to be >0.99 with a slope of 1.00 ± 0.01. Intra- and interday reproducibility of standards spiked into plasma and serum revealed a coefficient of variation <20%. Spike and recovery assessment showed recovery values of 80%–120% for all standards. Altered levels of sphingolipids from patients with hereditary sensory and autonomic neuropathy caused by pathogenic variants in SPTLC2 and hypomyelinating leukodystrophy related to variants in DEGS1 were detected, in agreement with trends reported in earlier studies confirming the utility of this pathway-centric method. Conclusions This method can serve as a useful tool to simultaneously monitor sphingolipids, enabling screening and diagnosis of inborn errors of ceramide metabolism.

Abstract Background The authors previously developed an artificial intelligence (AI) to assist cytologists in the evaluation of digital whole‐slide images (WSIs) generated from bile duct brushing specimens. The aim of this trial was to assess the efficiency and accuracy of cytologists using a novel application with this AI tool. Methods Consecutive bile duct brushing WSIs from indeterminate strictures were obtained. A multidisciplinary panel reviewed all relevant information and provided a central interpretation for each WSI as being “positive,” “negative,” or “indeterminate.” The WSIs were then uploaded to the AI application. The AI scored each WSI as positive or negative for malignancy (i.e., computer‐aided diagnosis [CADx]). For each WSI, the AI prioritized cytologic tiles by the likelihood that malignant material was present in the tile. Via the AI, blinded cytologists reviewed all WSIs and provided interpretations (i.e., computer‐aided detection [CADe]). The diagnostic accuracies of the WSI evaluation via CADx, CADe, and the original clinical cytologic interpretation (official cytologic interpretation [OCI]) were compared. Results Of the 84 WSIs, 15 were positive, 42 were negative, and 27 were indeterminate after central review. The WSIs generated on average 141,950 tiles each. Cytologists using the AI evaluated 10.5 tiles per WSI before making an interpretation. Additionally, cytologists required an average of 84.1 s of total WSI evaluation. WSI interpretation accuracies for CADx (0.754; 95% CI, 0.622–0.859), CADe (0.807; 95% CI, 0.750–0.856), and OCI (0.807; 95% CI, 0.671–0.900) were similar. Conclusions This trial demonstrates that an AI application allows cytologists to perform a triaged review of WSIs while maintaining accuracy.

Background and Objectives: We investigated the effects of using a BiZact™ device for tonsillectomy on operating time, intraoperative blood loss, postoperative bleeding rate, and pain through a meta-analysis of the relevant literature. Materials and Methods: We reviewed studies retrieved from the databases of PubMed, SCOPUS, Google Scholar, Embase, Web of Science, and Cochrane up to March 2024. The results were analyzed following PRISMA guidelines. Six studies that compared the outcomes of patients receiving perioperative BiZact™ tonsillectomy with those in control groups (cold steel dissection or bipolar tonsillectomy) were included for this analysis of the outcomes, which included intraoperative bleeding and time, postoperative pain, and frequency of postoperative bleeding. Results: The operative time (SMD −11.5985, 95%CI [−20.3326; −2.8644], I2 = 99.5%) in the treatment group was significantly reduced compared to the control group. However, BiZact™ showed no significant efficacy in reducing intraoperative bleeding when compared with the control group (SMD −0.0480, 95%CI [−1.8200; 1.7240], I2 = 98.6%). Postoperative pain on day 1 (SMD −0.0885, 95%CI [−0.4368; 0.2598], I2 = 98.9%), day 3 (SMD −0.2118, 95%CI [−0.6110; 0.1873], I2 = 99.5%), and later than day 7 (SMD 0.0924, 95%CI [−0.2491; 0.4338], I2 = 98.6%) in the treatment group was not significantly reduced relative to the control group. When compared to the control group, BiZact™ did not reduce the incidence of secondary postoperative bleeding control in the operation room (OR 0.5711, 95%CI [0.2476; 1.3173], I2 = 32.1%), primary bleeding (OR 0.4514, 95%CI [0.0568; 3.5894], I2 = 0.0%), or all postoperative bleeding events (OR 0.8117, 95%CI [0.5796; 1.1368], I2 = 26.3%). Conclusions: This study demonstrated that using the BiZact™ device for tonsillectomy significantly decreased the operative time but could not effectively reduce intraoperative bleeding or postoperative pain and bleeding.

Cardiovascular disease (CVD) is a significant health concern influenced by various determinants. Stigma and resilience have emerged as factors in CVD development and management. Women with HIV (WWH) have higher CVD rates than women without HIV. To improve cardiovascular health for WWH, a comprehensive understanding of how these factors interact, the understanding about individual awareness and willingness to engage in risk-reduction interventions are needed. Methods: As part of a study examining CVD risk among WWH aged >35 years old, 90-min focus groups were conducted (May 2022) in the English language. Focus groups aimed to elicit participants’ CVD risk knowledge and potential prevention strategies. Transcripts underwent a qualitative analysis. Results: Nineteen WWH participated in three focus groups. Participants experienced the following: (a) enacted stigma related to their HIV diagnosis (e.g., family, church member, healthcare staff); (b) a recent event (e.g., hospitalization of self/family, death in family, chest pain) triggered both heart health-promoting lifestyle changes and suboptimal health behaviors (e.g., COVID-19 pandemic: unhealthy snacking). Participants wanted to obtain more knowledge (“on a mission”) about CVD risk. In total, 100% expressed willingness to take medication or embark on other lifestyle changes to prevent future CVD events. Although participants identified preventative heart health behaviors (e.g., eating healthy foods; exercising; limiting stress, substances, and smoking), misconceptions were also identified (e.g., “catching” heart disease). Conclusions: Understanding the interplay of the different factors related to heart health is needed both at the provider and the patient level to inform interventions that reduce CVD risk amongst racial/ethnic minoritized women with HIV, living in the Southern region of the US.

Abstract Background A plant-based diet is associated with better survival among patients with nonmetastatic colorectal cancer (CRC), but its association in metastatic CRC is unknown. Methods Using an National Cancer Institute–sponsored trial (CALGB/SWOG 80405), we included 1284 patients who completed validated food frequency questionnaires at the initiation of metastatic CRC treatment. We calculated 3 indices: overall plant-based diet index (PDI), which emphasized consumption of all plant foods while reducing animal food intake; healthful plant-based diet index (hPDI), which emphasized consumption of healthful plant foods such as whole grains, fruits, and vegetables; and unhealthful plant-based diet index (uPDI), which emphasized consumption of less healthful plant foods such as fruit juices, refined grains, and sugar-sweetened beverages. We estimated the associations of 3 indices (quintiles) with overall survival (OS) and progression-free survival (PFS) using multivariable Cox proportional hazards regression. Results We observed 1100 deaths and 1204 progression events (median follow-up = 6.1 years). Compared with the lowest quintile, patients in the highest quintile of PDI had significantly better survival (hazard ratio [HR] for OS = 0.76 [0.62-0.94], Ptrend = .004; PFS = 0.81 [0.66-0.99], Ptrend = .09). Similar findings were observed for hPDI (HR for OS = 0.81 [0.65-1.01], Ptrend = .053; PFS = 0.80 [0.65-0.98], Ptrend = .04), whereas uPDI was not associated with worse survival (HR for OS = 1.16 [0.94-1.43], Ptrend = .21; PFS = 1.12 [0.92-1.36], Ptrend = .42). Conclusions Our study suggests that a plant-based diet, especially when rich in healthful plant foods, is associated with better survival among patients with metastatic CRC. The cause of survival benefits warrants further investigation.

Background: Assessment of orthopaedic surgery trainees is traditionally based on subjective evaluation by faculty. The recent push for value-based health care has placed a premium on improving patient outcomes. As a result, surgical training evaluations for orthopaedic trainees are evolving to include more objective measures to evaluate competency. Purpose: To develop and subsequently demonstrate the efficacy of a novel surgical skills assessment for orthopaedic sports medicine fellows. Study Design: Case series; Level of evidence, 4. Methods: A team of 14 fellowship-trained orthopaedic sports medicine surgeons developed objective scoring rubrics for anterior cruciate ligament reconstruction (ACLR) and rotator cuff repair (RCR) using a modified Delphi process. Rubrics were designed based on 10 surgical steps with a grading scale (1-5) based on core competencies with a maximum summative score of 50. Fourteen orthopaedic fellows across a regionally diverse group of sports medicine–accredited fellowship programs were invited to complete both an ACLR and RCR in a surgical skills laboratory at the beginning and end of their fellowship year. Individual surgical steps, overall performance, and total procedure time were evaluated by a single sports medicine surgeon for both sessions. Results: Thirteen of 14 fellows completed both pre- and post-fellowship assessments. For the ACLR procedure, the pre-fellowship mean summative score was 25.4 (SD, 4.4) and the post-fellowship mean summative score was 38.6 (SD, 4.1), which was a statistically significant improvement ( P < .001). For the RCR procedure, the pre-fellowship mean summative score was 26.6 (SD, 5.4) and the post-fellowship mean summative score was 38.8 (SD, 4.3), which was also a statistically significant improvement ( P < .001). The mean time to completion for the ACLR procedure was 82.3 minutes (SD, 4.3 minutes) pre-fellowship, which improved to 69.7 minutes (SD, 11.6 minutes) post-fellowship ( P = .002). The mean time to completion for the RCR procedure was 85.5 minutes (SD, 5.0 minutes) pre-fellowship, which improved to 76.4 minutes (SD, 7.0 minutes) post-fellowship ( P < .001). Conclusion: This surgical skills program represents the first standardized and reproducible instrument for the evaluation of 2 arthroscopic sports medicine procedures in the United States. Orthopaedic sports medicine fellows improved significantly in aggregate over their fellowship year with regard to the ACLR and RCR. The described program has the potential to serve as both a training tool and formal orthopaedic sports medicine fellow assessment.