Citations

Background: Total hip arthroplasty (THA) effectively restores mobility, reduces pain, and enhances the quality of life of patients of all ages. Despite its benefits, concerns regarding the long-term effects of high-impact activities and sports on implant longevity require further study. This study investigated the effect of activity level on long-term radiographic wear of highly cross-linked polyethylene (HXLPE) in young patients undergoing THA. Methods: Between 1999 and 2008, 785 patients (909 hips) aged ≤50 underwent primary THA using first-generation HXLPE liners from 4 different vendors with either metal or ceramic heads. Functional activity and participation questionnaires, including the Hip Injury and Osteoarthritis Outcome Score (HOOS Jr), University of California Los Angeles (UCLA) activity scale, and High-Activity Arthroplasty Score (HAAS), were surveyed in 2018 to 2019. The response rate was 44%. Radiographic linear wear rates were measured using the ROMAN software in patients who had completed questionnaires and had radiographs taken at least 10 years apart, leaving a final cohort of 249 patients (284 hips). Multivariate analyses were performed to determine the relationship between HXLPE wear rates and activity scores. Results: At the time of the survey, approximately 10% of the patients performed high-impact activities not-recommended by consensus guidelines. The HXLPE linear wear rate was 0.036 mm/year (SD: 0.026). Patients with higher activity levels, as measured on the continuous UCLA/HAAS activity scale, did not exhibit increased wear (β = -0.0009; p = 0.31). Stair climbing was correlated with increased wear rates (β = 0.0066; p = 0.004), whereas walking (β = 0.0005; p = 0.66) and running (β = 0.0017; p = 0.30) were not significantly correlated. Patients performing nonrecommended activities did not show increased wear rates compared with those performing recommended activities (β = 0.0063; p = 0.19). Conclusions: Linear wear rates of first-generation HXLPE were not related to functional activity or participation in high-impact activities. Future research should include longitudinal assessments of activity levels and data on other potential complications related to high-impact sports to provide robust evidence regarding recommended activity level postoperatively. Level of Evidence: Level III , Retrospective Comparative Study. See Instructions for Authors for a complete description of levels of evidence.

Abstract Background Primary aldosteronism (PA), a primary adrenal disorder leading to excessive aldosterone production by one or both adrenal glands, is a common cause of hypertension. It is associated with an increased risk of cardiovascular complications compared with primary hypertension. Despite effective methods for diagnosing and treating PA, it remains markedly underdiagnosed and undertreated. Objective To develop an updated guideline that provides a practical, clinical approach to identifying and managing PA to improve diagnosis rates and encourage targeted treatment. Methods The Guideline Development Panel (GDP), composed of a multidisciplinary panel of clinical experts and experts in systemic review methodology, used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to define 10 questions related to the diagnosis and treatment of PA. Systematic reviews were conducted for each question. The GDP used the GRADE Evidence to Decision (EtD) framework to consider contextual factors, such as stakeholder values and preferences, costs and required resources, cost-effectiveness, acceptability, feasibility, and the potential impact on health equity. Results We suggest that all individuals with hypertension be screened for PA by measuring aldosterone and renin and determining the aldosterone to renin ratio, and that subsequent clinical care be guided by the results. We suggest that individuals with PA receive PA-specific therapy, either medical or surgical. In individuals who screen positive for PA, we suggest (1) commencement of PA-specific medical therapy in individuals who do not desire or are not candidates for surgery and in situations where the probability of lateralizing PA (excess aldosterone produced by one adrenal) is low based on screening results; and (2) aldosterone suppression testing in situations when screening results indicate an intermediate probability for lateralizing PA and individualized decision making confirms a desire to pursue eligibility for surgical therapy. In those who test positive by aldosterone suppression testing, and in those in whom screening results show a high probability of lateralizing PA (obviating the need for aldosterone suppression testing), we suggest adrenal lateralization with computed tomography scanning and adrenal venous sampling prior to deciding the treatment approach (medical vs surgical). In all individuals with PA and an adrenal adenoma, we suggest performing a 1-mg overnight dexamethasone suppression test. We suggest the use of mineralocorticoid receptor antagonists (MRAs) over epithelial sodium-channel (ENaC) inhibitors in the medical treatment of PA. We suggest the use of spironolactone over other MRAs, given its lower cost and greater availability; however, all MRAs, when titrated to equivalent potencies, are anticipated to have similar efficacy in treating PA. Thus, MRAs with greater mineralocorticoid receptor specificity and fewer androgen/progesterone receptor-mediated side effects may be preferred in some situations. In individuals receiving MRA therapy, we suggest monitoring renin and, in those whose hypertension remains uncontrolled and renin is suppressed, titrating the MRA to increase renin. Conclusion These recommendations provide a practical framework for the diagnosis and treatment of PA. They are based on currently available literature and take into consideration outcomes that are important to key stakeholders. The goal is to increase identification of individuals with PA and, by initiating PA-specific medical or surgical therapy, improve blood pressure control and reduce PA-associated adverse cardiovascular events. The guidelines also highlight important knowledge gaps in PA diagnosis and management.

Abstract Introduction: Cystic Fibrosis (CF) is traditionally diagnosed through elevated sweat chloride levels followed by genetic testing. However, depending on types of specific CFTR gene mutations, sweat chloride test may not always be conclusive. This case study presents a unique instance of CF in a 50-year-old patient with negative sweat chloride levels who was later found to have CFTR dysfunction during the evaluation for worsening bronchiectasis, highlighting the diagnostic challenges posed by atypical presentations. Description: A 50-year-old female with a long-standing history of bronchiectasis and recurrent exacerbations was evaluated at our clinic. Initial sweat chloride testing yielded negative results (21 and 28 on two separate occasions), which made a CF diagnosis very unlikely. She was subsequently treated with standard airway hygiene measures while alternative diagnoses were explored. However, despite thorough work-up and management, her bronchiectasis continued to worsen, leading to genetic testing to complete the comprehensive evaluation of her condition. The CFTR mutation panel revealed the presence of G551D and D1152H (variants known to be associated with normal sweat chloride test). Despite the negative sweat chloride test, the patient's clinical presentation, including bronchiectasis, recurrent exacerbations, and the identified CFTR mutations, supported a diagnosis of CF. The patient has since responded positively to combination therapy with Elexacaftor, Tezacaftor and Ivacaftor, which is indicated for her genotype. Discussion: This case underscores the limitations of relying solely on sweat chloride testing for diagnosing CF, particularly in patients with atypical CFTR mutations. Variants like D1152H have been reported with normal sweat chloride levels, challenging traditional diagnostic paradigms. Genetic testing plays a crucial role in these cases by identifying mutations that may still lead to significant CFTR dysfunction. The patient's improvement on CFTR modulator therapy further supports the role of genotype-driven treatment strategies in CF care. This case highlights the need for a broader diagnostic approach, including comprehensive genetic testing and clinical correlation, especially for patients presenting with non-classical CF features. It contributes to the growing understanding that CF is a spectrum disorder with varied clinical and biochemical presentations, emphasizing the importance of individualized diagnosis and treatment strategies to optimize patient outcomes.

Listing and transplanting patients with acute liver failure (ALF) is challenging, requiring rapid assessment of the likelihood of recovery. The availability of a large number of ALF liver explants, along with their clinical data, afforded an opportunity to retrospectively evaluate liver transplantation (LT) decision-making. We hypothesized that, with the benefit of hindsight, a small number of patients might have recovered without LT. Three hundred liver explants from ALF patients of varying etiologies who had undergone LT over 22 years in the Acute Liver Failure Study Group registry were reviewed for histopathological features and degree of necrosis by a committee of 8 hepatopathologists. A second committee of 8 experienced transplant hepatologists independently reviewed clinical data on these same 300 patients and retrospectively scored the likelihood that each patient required transplantation. Only 3 (1%) of those reviewed by the Clinical Committee were considered to “Definitely” not require liver grafting, while an additional 10 (3.3%) were deemed to “Possibly” not require transplantation (Not Likely Group, N=13). There was no difference in the degree of necrosis in explants in these groups, when compared to the remaining Likely Group, N=287 (95.6%), except in acetaminophen (APAP)-associated ALF, where the degree of necrosis was more uniformly graded as severe, correlating with the need for transplantation. Virtually every patient undergoing LT for ALF retrospectively appeared to need their transplant, based on expert clinical consensus review. Overall, there was poor correlation between clinical severity and apparent degree of necrosis seen in the 300 liver explants, except perhaps for APAP subjects.

Abstract Objective Rare large B-cell lymphomas (LBCLs) present with concurrent or subsequent lymphomatous effusion (solid-effusion LBCL, SE-LBCL), which may have an inferior prognosis compared with their noneffusion counterpart. In addition, the relationship between SE-LBCL and human herpesvirus 8–negative effusion-based LBCL (EB-LBCL) remains unclear. Methods We collected 141 cases of SE-LBCL and a control cohort of 101 cases of stage IV solid-only LBCL. The clinicopathologic features were analyzed and compared between SE-LBCL and solid-only LBCL. Results Patients with SE-LBCL had a median age of 67 years with a male-to-female ratio of 1.3:1. Eighty-six patients had concurrent solid lymphoma and lymphomatous effusion, whereas 55 developed lymphomatous effusion subsequently. Most cases involved the pleural cavities (79%, 112/141), followed by the peritoneal (21%, 29/141) and pericardial (11%, 16/141) cavities. BCL6, CD10, and MUM1 were expressed in 77% (90/117), 46% (60/130), and 61% (58/95) of cases, respectively, and 58% (71/123) were subclassified into the germinal center B-cell (GCB) subtype. Rearrangements of BCL2, BCL6, and MYC were detected in 42% (31/73), 35% (22/63), and 40% (35/88), respectively, and 22% (19/87) had both MYC and BCL2 rearrangements. The patients with SE-LBCL had a dismal prognosis, with a median survival of 5.7 months, which was significantly worse than solid-only LBCL (147.5 months; P < .0001). Conclusions The pathologic features of SE-LBCL were similar to those of solid-only LBCL but distinct from those of EB-LBCL; in particular, lymphomatous effusion was an independently adverse prognostic factor in LBCL. Our study underscores the need for surveillance of lymphomatous effusion during LBCL staging and development of effective therapeutic regimens for SE-LBCL.

Background Secondary aortoenteric fistulas (SAEF) following endovascular aortic repair (EVAR) is an extremely rare event but life threatening. Our review offers comprehensive knowledge on pathophysiology, clinical presentation, diagnosis, and treatment options. Aim To summarize the current literature regarding pathophysiology, clinical, diagnostic and therapeutic approach of aortoenteric fistulas secondary to EVAR. Methods We performed a literature search in Pubmed/MEDLINE to identify the literature published about SAEF after EVAR. Cases were summarized in a table and prevalences. Other relevant literature was included in the results sections. Results A total of 35 reports (single cases and small series) with 45 patients were included. SAEF after EVAR can result from infection, inflammation, or mechanical factors. Clinical presentation is often non-specific, ranging from a gastrointestinal herald bleed to hemorrhagic shock, or malaise and general infection-related symptoms. Cross-sectional imaging plays a critical role in diagnosing SAEF. The treatment approach involves a multidisciplinary team approach and requires broad-spectrum intravenous antibiotics, endovascular intervention for urgent hemorrhage control, and open surgical intervention for definitive repair. Long-term antimicrobial therapy is essential to avoid reinfection. Conclusions SAEF following EVAR represents a complex, life-threatening condition with limited evidence-based management strategies. Given the growing prevalence of endovascular procedures, comprehensive knowledge of SAEF is crucial for all health care providers to improve early diagnosis and outcomes.

Abstract Objective Glucocorticoid withdrawal syndrome (GWS) may develop in patients following successful surgery for endogenous hypercortisolism. Effective strategies to minimize GWS and improve quality of life (QoL) are currently lacking. We aimed to determine the impact of hydrocortisone vs prednisone therapy on GWS and QoL during the first 12 weeks postsurgery. Methods Single-center prospective cohort study (2019-2024) of adults with endogenous hypercortisolism who developed postoperative adrenal insufficiency and treated with either prednisone or hydrocortisone. Quality of life was assessed with Short Form-36 (SF-36) and Cushing QoL questionnaires at baseline and at 12 weeks postsurgery. GWS was assessed using weekly AddiQoL questionnaires for the first 12 weeks postsurgery. Results Of 165 patients, 101 (61%) were treated with hydrocortisone and 64 (39%) with prednisone. At baseline, no group differences were found in the hypercortisolism subtype, comorbidities, or QoL assessments. At follow-up, no group differences in final total daily hydrocortisone equivalent dose were seen. When adjusting for the baseline QoL assessment, patients treated with prednisone demonstrated a higher degree of improvement in their QoL, particularly in the SF-36 mental component score (estimate 0.33, 95% CI, 0.04-0.63), SF-36 role-emotional limitation (estimate 0.52, 95% CI, 0.2-0.84), and SF-36 body pain (estimate 0.31, 95% CI, 0.07-0.56) subcomponents. In the multivariable analysis of age, sex, body mass index, glucocorticoid type, baseline clinical severity score, and baseline QoL assessment, prednisone therapy was an independent predictor of better SF-36 mental component at 12 weeks postsurgery. Conclusions Prednisone therapy was associated with better mental health QoL than hydrocortisone at 12 weeks postsurgery in patients with hypercortisolism.

AbstractAlthough guidelines have historically recommended deferring decisions about learning genomic information for conditions not actionable in childhood until adulthood, youth have increasing access to personal genomic information through research, clinical, and direct‐to‐consumer testing. However, little is known about young people's reactions to, and perceived future utility of learning genomic information actionable in adulthood. We conducted qualitative interviews with 28 youth ages 15–22 without clinical indications for genetic screening who, through enrollment in a genomic decision‐making research study, learned they were carriers of an autosomal recessive condition, or anticipated being carriers but received negative results. Semi‐structured interviews occurred virtually between 3 and 16 months after the return of results. Interpretative description guided deductive and inductive coding of transcripts. Of the 28 participants, 21 received positive carrier results, and 7 received negative results. Although some carriers felt the result was unexpected, they expressed relief overall and did not feel worried about their result. Participants with negative results also felt relief about their results. All participants correctly described what a carrier result means, but some carriers could not remember the condition associated with their result. No participant regretted learning personal genomic information, and all reported their results helped them better understand risks to future children. Carriers who perceived the condition for which they were carriers as more severe and/or those familiar with the condition were more likely to remember their result and consider future reproductive options. Carriers also felt testing at their respective age allowed increased familiarity with results and more time to gather information and decide on the personal utility of the information. Our findings suggest early access to genomic information for some youth may allow integration of carrier information over time with minimal adverse effects. More research is needed to assess long‐term outcomes among carriers.

PURPOSE Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We analyze the role of germline DICER1 status in outcomes of ovarian SLCT. METHODS Patients with SLCT were enrolled in the International Pleuropulmonary Blastoma/ DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and those with known germline DICER1 status were selected for analysis. RESULTS Of 162 patients with SLCT, 60% had a germline DICER1 pathogenic or likely pathogenic (P/LP) variant. The adjusted 3-year recurrence-free survival (RFS) was 87.2% (95% CI, 79.4 to 95.8) for patients with a germline DICER1 P/LP variant compared with 78.1% (95% CI, 66.4 to 91.9) for those without a germline DICER1 P/LP variant ( P = .043). The adjusted 3-year and 5-year overall survival (OS) was 93.9% (95% CI, 87.3 to 100.0) for those with a germline DICER1 P/LP variant compared with the 3-year OS of 91.3% (95% CI, 83.4 to 100.0) and the 5-year OS of 78.2% (95% CI, 63.8 to 95.9) for those without a germline DICER1 P/LP variant ( P = .021). Among patients with a germline DICER1 P/LP variant, the risk of a subsequent, nonrecurrent event was 36.2% (95% CI, 21.4 to 48.1) within 10 years. Previous/concurrent and subsequent neoplasms were rare among those without a germline DICER1 P/LP variant. CONCLUSION This cohort study of patients with SLCT demonstrated that those with germline DICER1 P/LP variants had superior RFS and OS even when adjusting for other prognostic factors. Beyond prognostic implications of a germline DICER1 P/LP variant, germline testing helps identify patients at risk of subsequent neoplasms, including metachronous SLCT.