Citations

This essay describes diagnostic criteria for and thoracic imaging appearances of acute and chronic coccidioidal pneumonia, unusual disease manifestations, and disseminated disease appearances.

Abstract Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Although patients with FL have high response rates to therapy, most develop increasingly resistant disease. In addition, transformation into an aggressive lymphoma is associated with unfavorable outcomes. Many novel agents are under investigation, and early clinical data are encouraging. Aligning treatment with the underlying tumor biology and sequencing of therapies remain key clinical challenges. At the Lymphoma Research Foundation’s biannual 2024 Follicular Lymphoma Scientific Workshop, experts convened to discuss the role of chemotherapy in the context of new therapies, the impact of early progression on treatment sequencing, novel end points in clinical trials, disease biology and the tumor microenvironment, and new treatments on the horizon. This report focuses on updates in FL biology, first-line treatment, the role of progression of disease in 24 months, clinical trial design, and redefining cure in FL.

Key Points Genetic testing in CKD showed diagnostic and clinical utility in the year following reporting of test results. Genetic testing was helpful for or changed management in 86% of patients with a positive finding and 42% with a negative finding. Clinical utility was seen across 12 clinical cohorts, including CKD of unknown etiology and hypertension or diabetes-related nephropathy. Background CKD is a significant public health burden, affecting >800 million people worldwide with significant cost to the health care system. CKD is a disease process with substantial genetic and phenotypic heterogeneity that can obscure a definitive diagnosis, resulting in suboptimal management. Recent guidelines support greater adoption of genetic testing in CKD. We assessed the diagnostic and clinical utility in the year following broad-panel CKD genetic testing. Methods The Renasight Clinical Application, Review, and Evaluation (RenaCARE) study (NCT05846113) was a single-arm, interventional, prospective, multicenter study evaluating the utility of genetic testing with a 385-gene panel on the diagnosis and management of CKD. Clinical history was collected before testing, and nephrologists responded to questionnaires at both 1 month and 1 year after testing. The impact of genetic testing on CKD diagnosis and management were assessed in active study patients at the 1-year time point. Results In a cohort of 1388 CKD patients with 13 pretest clinical categories of CKD, 335 (24%) patients had a positive genetic finding; 1174 had a questionnaire completed at 1 year and were included in the analysis. Genetic testing was reported helpful for clinical management and/or led to a change in management in 86% of patients with a positive test finding and 42% of patients with a negative test finding. In addition, genetic testing resulted in a change in the physician estimation of the 5-year prognosis for 55% of patients with a positive test finding and 18% of those with a negative test finding. Conclusions Supporting the previous results of the RenaCARE study at 1 month, this report demonstrated that genetic testing was helpful in the clinical management and estimated prognosis of patients with CKD. Clinical Trial registry name and registration number: ClinicalTrials.gov, NCT05846113.

Suzetrigine is a unique, nonopioid oral analgesic that selectively inhibits voltage-gated sodium channels in peripheral nerves. The Food and Drug Administration (FDA) recently approved it, and we present the first successful use of suzetrigine in a 16-year-old boy with hereditary neuropathy who underwent foot reconstruction surgery. His postoperative pain management plan included a sciatic nerve catheter, a 14-day course of suzetrigine, opioids, and home medications. His pain was well controlled with no side effects. Within 24 hours of stopping suzetrigine, the patient’s pain rapidly intensified, suggesting suzetrigine’s effectiveness in postoperative pain management in an adolescent patient with neuropathy.

PURPOSE Although most patients with follicular lymphoma (FL) can expect an indolent course, progressive lymphoma remains the primary cause of death during the first decade after diagnosis. Progression of disease within 24 months (POD24) of starting first-line (1L) immunochemotherapy defines a high-risk population with poor survival, but better risk stratification at diagnosis is needed. METHODS The FLIPI24 model was developed and internally validated to predict 24-month event rates using individual data from 4,485 patients treated with 1L immunochemotherapy from 10 observational cohorts of FL. Overall and cause-specific survival was further evaluated in FLIPI24 risk groups. External validation in the 1L immunochemotherapy setting was performed using the prospective observational Lymphoma Epidemiology of Outcomes (LEO) cohort (N = 565) and three randomized phase III trials (N = 3,192); extension to all patients with FL (any 1L therapy) was performed in the LEO cohort (N = 1,445) and its Molecular Epidemiology Resource subcohort (N = 1,074). RESULTS The FLIPI24 model uses age and four blood-based variables (hemoglobin, lactate dehydrogenase, beta-2 microglobulin, and WBC count). FLIPI24 showed consistent performance across validation and extension data sets, which was superior to existing prognostic tools. Across the four external immunochemotherapy validation data sets, patients with high-risk FLIPI24 (23%-32% of patients) had significantly higher 24-month event rates (22%-35%) and inferior 5-year overall survival (77%-83%) compared with patients with low-risk FLIPI24 (29%-31% of patients, 24-month event rates: 10%-12%; 5-year OS: 96%-97%). Results were consistent when evaluating lymphoma-related death and when extended to all patients with FL. CONCLUSION The FLIPI24 model robustly stratifies, at diagnosis, patients with FL at increased risk of lymphoma-related death versus patients with very low lymphoma-related mortality during the first decade after diagnosis. FLIPI24 can be used to enrich future clinical trial designs in newly diagnosed FL.

Abstract Anaplastic large cell lymphomas (ALCLs) are CD30+ T-cell lymphomas that share pathologic features but differ in presentation, outcome, and genetics. Current classification incorporates clinical presentation and anaplastic lymphoma kinase (ALK) status but inadequately addresses molecular heterogeneity and therapeutic vulnerabilities. We studied 689 patients with ALCL in the LLMPP (Lymphoma/Leukemia Molecular Profiling Project) and performed expert consensus review, genetic subtyping (ALK, DUSP22, TP63, and triple negative), and immunohistochemistry for phosphorylated STAT3Tyr705. RNA sequencing with unsupervised gene expression profiling in 393 patients identified 2 main molecular types of ALCL that could be predicted with 91% accuracy based on the presence (type I) or absence (type II) of phosphorylated STAT3Y705 expression. Type I ALCLs included ALK+ ALCL and a subset of triple-negative ALCLs (TN-I); type II ALCLs included tumors with DUSP22 and/or TP63 rearrangements and the remaining triple-negative ALCLs (TN-II). Type I ALCLs were enriched for JAK-STAT3, whereas type II ALCLs were enriched for non–tyrosine kinase pathways, particularly epigenetic regulators such as EZH2. Immunohistochemistry showed overexpression of EZH2 and its trimethylated substrate H3K27. Prognosis in systemic ALCL was favorable for DUSP22-rearranged ALCL (5-year overall survival, 95%) and ALK+ ALCL (88%), intermediate for triple-negative ALCL (TN-I, 52% and TN-II, 37%), and poor for TP63-rearranged ALCL (0%). We introduce an integrated molecular classification that preserves currently diagnosed ALCL entities but identifies 4 molecularly distinct ALK− ALCL subtypes (DUSP22-rearranged, TP63-rearranged, TN-I, and TN-II). This classification can be easily implemented on paraffin tissue in routine practice or clinical trials, and stratifies ALCL into diagnostically, prognostically, biologically, and potentially therapeutically relevant subtypes.

Objective: To review the pharmacology, usage, efficacy, and safety of fenfluramine in treating seizures in pediatric patients with Lennox-Gastaut syndrome or Dravet syndrome. Data sources: The PubMed database was searched for studies using the search terms “Lennox-Gastaut Syndrome,” “Dravet Syndrome,” “fenfluramine,” and “Fintepla©.” Study selection and data extraction: Articles were selected based on the following criteria: published in English, published between January 1950 and September 2025, and included clinical relevancy for pharmacology, efficacy, and adverse events. Data synthesis: In a phase 3 trial, patients with Lennox-Gastaut syndrome experienced a median 26.5% decrease in frequency of drop seizures when taking the 0.7 mg/kg/d dose. In a 2-part phase 2 trial, 54% of patients with Dravet syndrome concurrently taking stiripentol experienced a >50% decrease in monthly seizures at a dosage of 0.4 mg/kg/d; 72.9% of patients with Dravet syndrome not concurrently taking stiripentol experienced a >50% decrease in monthly seizures at a dosage of 0.7 mg/kg/d. Most common adverse effects in both trials included lethargy, decreased weight, and decreased appetite. Relevance to patient care and clinical practice: Fenfluramine’s dual mechanism of action makes it uniquely suited to reduce seizure activity after previous failures in treatment. Some providers are hesitant to prescribe fenfluramine due to its historical association with severe cardiovascular risks. However, proper dosage and titration, as well as adherence to the Risk Evaluation and Mitigation Strategy program can sufficiently mitigate risk for the outcome of seizure reduction and increased quality of life. Conclusions: As seen through the results of multiple clinical trials, fenfluramine can provide significant seizure reduction for Lennox-Gastaut and Dravet patients with treatment-resistant seizures. Risks can be mitigated through adherence to proper programs and schedules, and can provide enough benefits to outweigh risks in patients with particularly resistant epilepsies.

Aims Data on revision of unicompartmental knee arthroplasty (UKA) to total knee arthroplasty (TKA) are limited by low patient numbers and short-term follow-up. This study evaluated the mid-term outcomes of revision of UKA to TKA focusing on implant survival, radiological results, and clinical outcomes in a large series. Methods We identified 235 revisions of UKA to TKA performed between 1995 and 2022 utilizing our institutional total joint registry. The mean age was 65 years (SD 10), mean BMI was 32 kg/m 2 (SD 6), and 50% were female (n = 118). The most common indications for revision were aseptic loosening (37%; n = 83), progression of arthritis in adjacent compartments (35%; n = 81), and unexplained pain (20%; n = 47). The mean time from UKA to revision to a TKA was four years (26 days to 15 years). Posterior-stabilized constructs were used in 78% of the revisions (n = 184), varus-valgus constrained implants in 14% (n = 33), and cruciate-retaining implants in 7% (n = 16). Metaphyseal fixation devices were used in 8% of cases (n = 18) and augments in 31% (n = 73). Kaplan-Meier implant survival analyses were performed, radiographs reviewed, and clinical outcomes were measured with Knee Society Scores (KSSs). Mean follow-up was eight years (2 to 25). Results The five-year survival free of any re-revision was 93% (95% CI 89 to 97). There were 17 further re-revisions with femoral and/or tibial aseptic loosening (n = 7), periprosthetic joint infection (n = 4), and stiffness (n = 2) being the most common indications. The five-year survival free of any reoperation was 87% (95% CI 83 to 92). Stiffness (n = 7) and unresurfaced patellar clunk/crepitus (n = 4) were the most common indications for reoperations without implant exchange. There were 25 nonoperative postoperative complications, most commonly stiffness (n = 5), flexion instability (n = 4), and haematoma (n = 4). No unrevised TKAs showed signs of radiological loosening. KSS function score improved from 54 (SD 18) to 69 (SD 26; p = 0.003). Conclusion In this large series of 235 revisions of UKA to TKA, the five-year survival of the TKAs free of re-revision was good. Our data suggest that the implant survival and clinical outcomes were inferior to primary TKA. Tibial component aseptic loosening was the most common reason for re-revision. Cite this article: Bone Joint J 2025;107-B(12):1281–1287.