Citations

ABSTRACT Background Cytomegalovirus (CMV) infection is among the most common infections after solid organ transplantation and leads to high rates of morbidity and mortality. With the proliferation of large, claims‐based datasets, there is a need to assess the validity of ICD‐10‐CM codes in identifying CMV infection. Methods We conducted a retrospective cohort study of solid organ transplant recipients (SOTRs) from a regional health system who underwent first transplantation between January 1, 2016, and June 30, 2025, had at least 30 days of post‐transplant follow‐up, and had known donor/recipient CMV serostatus. We performed cross‐sectional and time‐to‐event analyses comparing the test performance of B25 ICD‐10‐CM codes in identifying CMV infection, clinically significant CMV infection (csCMVi), CMV disease, and CMV DNA reaching various thresholds. Results Of 8169 SOTRs, 3084 (37.8%) had B25 coded during follow‐up. In addition, 4287 (52.5%) developed CMV infection, 2356 (28.8%) csCMVi, 297 (3.6%) CMV disease, and 1669 (20.4%) CMV DNA ≥ 1000 IU/mL. B25 codes were most specific to any CMV infection (88.5%), most sensitive to CMV DNA ≥ 100 000 IU/mL (98.2%), and csCMVi had the highest Youden's Index (0.651; sensitivity 84.1%, specificity 81.0%). Multivariable Cox regression provided similar results but with variations in effect measure between ICD‐10‐CM codes and clinical CMV definitions. Conclusions ICD‐10‐CM codes showed modest performance in identifying CMV infection, most closely resembling csCMVi. ICD‐10‐CM codes poorly reflect CMV severity, however, and may overestimate CMV infection by some clinical definitions. These limitations should be considered when using CMV diagnosis codes for claims‐based studies of SOTRs.

PURPOSE Detection of bone marrow disease has been a major component of rhabdomyosarcoma (RMS) staging with bilateral bone marrow aspirates/biopsies (BMAB) from the iliac crests considered the diagnostic gold standard. This study's goal was to determine if 2- 18 F-labeled fluorodeoxyglucose positron emission tomography/computed tomography ([ 18 F]FDG PET/CT) or PET/magnetic resonance imaging (MRI) may replace BMAB in RMS staging. METHODS Patients were recruited in Europe and North America. Medical records, FDG PET/CT or FDG PET/MRI (PET), and BMAB reports were collected retrospectively. Images were re-reviewed by nuclear medicine physicians at the patients' home institutions if PET reports indicated increased FDG uptake at bone/bone marrow sites or if tumor cells were detected in bone marrow samples. RESULTS PET imaging and BMAB were performed before chemotherapy and tumor resection in 301 patients with FDG-avid RMS. Bone marrow metastases were detected by PET and BMAB in 54, by PET only in 24, and by BMAB only in one of 301 patients with FDG-avid primary tumors. Absence of bone marrow metastases was confirmed by PET and BMAB in 222 of 301 patients. These observations translated into 98% sensitivity and 90% specificity for PET in detecting bone marrow metastases when BMAB was considered as gold standard. FDG-avid marrow disease was patchy (1-5 foci) in one third of cases. Patients with marrow disease indicated by PET and BMAB had more FDG-avid bone marrow foci, more metastatic sites, and lower survival than those with marrow disease indicated by PET only, suggesting more advanced disease stages. CONCLUSION Bone marrow sampling may be omitted in patients without evidence of FDG-avid bone marrow disease by PET. If there are FDG-avid bone marrow lesions, further investigation by MRI and/or biopsy should be considered.

Background. The VPS35 p.D620N variant causes autosomal dominant Parkinson's disease (PD) and has been shown to activate the LRRK2 kinase pathway, resulting in increased Rab substrate phosphorylation in peripheral immune cells and elevated urinary bis(monoacylglycero)phosphate (BMP) levels. Recently, a VPS35 variant of unknown significance (c.959C>T; p.A320V) was described in two late-onset sporadic PD patients. Methods. We ascertained a family from the Canary Islands in which six siblings were chronically exposed to high doses of pesticides. Three siblings developed levodopa-responsive, akinetic-rigid PD, while the other three remained unaffected. Whole-exome sequencing was performed in the three affected siblings. The frequency of the resulting candidate variant was assessed in 23,327 PD patients and 9,235 controls from four independent cohorts. Members of this pedigree and unrelated controls were assessed for LRRK2 kinase activity in monocytes and neutrophils and BMP levels in urine. Results. The three affected siblings were all heterozygous for p.A320V, whereas the three unaffected siblings did not carry the variant. In the combined PD case-control cohort, p.A320V was identified in six patients and one control. However, unlike p.D620N, heterozygous carrier status for p.A320V was not associated with increased LRRK2 kinase activity or elevated urine BMP levels. Conclusions. While VPS35 p.A320V co-segregated with PD in this family, it did not exhibit the characteristic LRRK2-associated biomarker signature observed in VPS35 p.D620N carriers. It is possible that p.A320V exerts a subtle effect on VPS35 function that was not captured by the assays performed and that chronic pesticide exposure contributed to disease penetrance in this pedigree.

Primary mediastinal B-cell lymphoma (PMBCL) is a rare form of large B-cell lymphoma (LBCL) with around 90% of patients cured with frontline treatment. For relapsed or refractory (R/R) disease, the optimal treatment is unclear. CD19 chimeric antigen receptor-T cell (CAR-T) has been established as the preferred second line (2L) treatment for primary refractory or early relapsing LBCL based on the overall survival benefits observed in the landmark phase III trials. However, PMBCL patients were underrepresented on these pivotal studies. This study evaluated outcomes of 252 patients treated with 2L therapies for R/R PMBCL at 14 US institutions between 2001 and 2025. Platinum-based salvage with intent to proceed to high dose therapy and autologous stem cell transplant (HDT/ASCT) (platinum cohort) and CD19 CAR-T (CAR-T cohort) were given as 2L therapy in the real-world setting in 157 and 26 patients, respectively. Overall response rate (ORR), complete response (CR) rate and median progression-free survival (PFS) were significantly higher in the CAR-T cohort compared with the platinum cohort (ORR: 91.3% vs 44.2%, p <0.001; CR 65.2% vs 14.7%, p<0.001; median PFS not reached vs 3.5 months, hazard ratio (HR) 0.28, 95% CI 0.15-0.54, p=0.001). No significant difference was observed in overall survival. This study demonstrated superior response rate and PFS of CD19 CAR-T over platinum-based salvage with intent to proceed to HDT/ASCT as 2L treatment for R/R PMBCL.

Background New antiamyloid therapies (AAT) for treating patients with early Alzheimer disease (AD) have become available in the past 3 years. Although AAT can be beneficial in slowing progression of AD, they also come with potentially serious side effects, particularly for patients requiring anticoagulation or thrombolysis for cardiovascular conditions. Given that most patients with AD are older and likely to have cardiovascular risk factors, there is urgent need for additional guidance for clinicians about potential risks and benefits associated with AAT for patients with cardiovascular comorbidities, best practices for management of these patients, and special considerations with respect to emergency evaluation and treatment of patients on AAT who develop acute neurological symptoms. Methods The American Heart Association convened 75 multidisciplinary experts for the Amyloid‐Related Imaging Abnormalities Summit: Cardiovascular and Stroke Considerations for β‐Amyloid Immunotherapy in AD in July 2025. These experts were divided into 8 work groups to evaluate the current evidence related to AAT usage in patients with cardiovascular risk factors and conditions and develop consensus‐based guidance for clinicians. Results This statement outlines the outcomes of the Summit, including considerations for prescribers, primary care professionals, emergency personnel, and health care system stakeholders. These considerations are intended to improve identification of patients as appropriate candidates for AAT, management of patients with co‐occurring AD and cardiovascular conditions, and their emergency evaluation and treatment. The statement also includes guidance for shared decision‐making, implementation of system changes for improving dementia care, and recommendations for future research and data collection to add to the body of evidence for treating patients with concomitant AD and cardiovascular conditions. Conclusions Building on lessons learned from the establishment of stroke systems of care, the consensus‐based considerations outlined in this document can serve as a foundation for AD systems of care aimed at ensuring optimal use of these ground‐breaking therapies.

The NCCN Guidelines for Survivorship offer guidance for health care providers who care for survivors of adult-onset cancer. These guidelines include screening, evaluation, and treatment recommendations for common physical and psychosocial problems resulting from cancer and its treatment and provide a framework for care coordination. They also present guidance for helping cancer survivors to enhance their wellness and maintain a healthy lifestyle. This article summarizes the panel’s current recommendations and recent updates regarding anxiety, depression, distress, and trauma in cancer survivors.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of certain sites within the body. Pleural mesothelioma is the most common type and represents approximately 85% of mesotheliomas. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for evaluation and treatment in patients with pleural mesothelioma. The NCCN Guidelines will continue to be updated annually based on available clinical evidence and panel consensus.

ABSTRACT Background Few studies have examined pretransplant CD4 count and risk of post‐kidney transplant (KT) infection in persons with HIV (PWH). Methods This multi‐center, retrospective cohort study included adult PWH undergoing KT from 2004 to 2019. The primary outcome was infection in the first year post‐KT in PWH with pretransplant CD4 < 350 cells/µL versus CD4 ≥ 350 cells/µL. Relative risk was assessed using modified Poisson modeling. Restricted mean survival time analysis was used to assess 5‐year posttransplant outcomes. Results Of the 75 patients included, 27% had a pretransplant CD4 < 350 cells/µL. Those with CD4 < 350 versus CD4 ≥ 350 were more likely to be hospitalized for infection in the first year (55% versus 16%, p = 0.001). There were no significant differences in relative risk of infection in the first‐year posttransplant (RR: 1.31, p = 0.053), 5‐year overall survival (87.5% vs. 93%, p = 0.49) or 5‐year graft loss (29.4% vs. 23.1%, p = 0.61) betweengroups. Conclusion These findings suggest that pretransplant CD4 count alone may not reflect the true risk of post‐KT infection in PWH.