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Diagnosing pulmonary rheumatoid nodules (RN) is challenging because they are rare and share clinical, radiologic, and histopathologic features with other necrotizing granulomatous diseases such as infectious granulomas (IG) and granulomatosis with polyangiitis (GPA). Herein, we revisit the histopathologic features of RN and the findings in the adjacent lung tissue, in comparison with IG and GPA, to identify distinguishing features. Twenty-eight cases with surgically resected RN evaluated at our institution (1991 to 2024), 33 IG (10 mycobacterial infection, 10 histoplasmosis, 13 coccidiomycosis), and 10 GPA cases were included in the study. All available slides with H&E and special stains were reviewed for various histologic parameters within the nodules and in surrounding lung tissue. Many histopathologic features of RN overlap with the necrotizing granulomas seen in infections and GPA. However, some findings in the adjacent lung tissue showed significant differences. The lack of airspace granulomas/non-necrotizing granuloma and the absence of necrotizing vasculitis in the setting of RN can help to differentiate between infection cases and GPA, respectively. Given their considerable overlap, correlation with clinical context, serologic and microbiologic studies, as well as careful evaluation of special stains is crucial in the diagnosis of RN.

OBJECTIVE Previous research suggests elective surgical procedures performed later in the week have worse outcomes. This study investigated whether the day of the week on which elective anterior cervical discectomy and fusion (ACDF) surgery was performed impacts clinical outcomes. METHODS Using data from the Quality Outcomes Database, a nationwide, multicenter prospective registry, this study included patients undergoing elective ACDF for cervical spondylosis. Patients were categorized into groups based on the surgery day (early week, Monday and Tuesday; late week, Thursday and Friday). Analyzed outcomes included postoperative complications, readmissions, reoperations, and patient-reported outcomes. Statistical methods included the independent t-test, Pearson’s chi-square test, and multivariable logistic regression. RESULTS The study analyzed 19,818 patients, with 41.7% undergoing surgery early in the week and 36.9% later. There were no significant differences in 30-day mortality, readmissions, or reoperations between the two groups. Early-week surgical procedures were associated with a higher incidence of postoperative dysphagia requiring nasogastric tubes (0.6% vs 0.3%, p = 0.02) and a higher incidence of vocal cord paralysis (0.5% vs 0.3%, p = 0.01). The data indicate a surgical selection bias with more complex surgical procedures and higher risk patients typically scheduled earlier in the week, which likely contributed to the increased rates of dysphagia. Conversely, patients who underwent operations on Fridays were more likely to be discharged on the same day compared to those earlier in the week (p = 0.02), without a significant difference in length of stay overall. Surgical procedures performed later in the week were more likely to be performed at ambulatory surgical centers rather than inpatient facilities (p < 0.01), indicating a strategic selection of healthier patients for end-of-week procedures. CONCLUSIONS The day of elective ACDF surgery does not affect mortality, readmissions, or reoperation rates. However, early-week surgical procedures may see slightly higher rates of postoperative dysphagia and vocal cord paralysis, likely due to the scheduling of more complex cases or higher risk patients during these days. Overall, the authors’ data confirm that day of surgery does not influence overall patient recovery significantly. This information is useful for surgical planning and for providing patient reassurance that the day of the week does not significantly impact surgical outcomes.

Background: Many surgeons recommend weight loss for patients with obesity before total joint arthroplasty (TJA), but few studies have evaluated weight loss interventions. This study compared weight loss using a remote dietitian and a mobile application (app) with weight loss using standard care for patients with severe obesity before TJA. Methods: This multicenter randomized controlled trial included 60 subjects with a body mass index (BMI) of 40 to 47 kg/m 2 who had been scheduled for primary total hip or knee arthroplasty from September 2019 to January 2023. The mean age was 61 years, 67% were women, and the mean BMI was 44 kg/m 2 . The control subjects (n = 29) received standard care; the intervention subjects (n = 31) completed video calls with dietitians and used a mobile app for 12 weeks preoperatively. Weights and surveys were collected at baseline and 12 weeks, with 87% follow-up. Weight loss, patient-reported outcomes, complications, revisions, and reoperations were compared. The mean follow-up was 1.8 years. Results: The intervention subjects lost more weight (−4.1 versus −2.1 kg, p = 0.22) and had larger decreases in BMI (−1.4 versus −0.9 kg/m 2 , p = 0.36 than the controls, but not significantly so. The intervention subjects had higher odds of achieving a BMI of <40 kg/m 2 (odds ratio = 1.9, p = 0.44), but not significantly so. There were no significant differences in the mean change in the Hip disability and Osteoarthritis Outcome Score, the Knee injury and Osteoarthritis Outcome Score, or the Lower Extremity Activity Scale score. At baseline, only 11% had seen a dietitian in the last 3 months. Most subjects (83%) felt that video calls were helpful. There were no differences in complications between the groups; there was a patellar fracture in the control group and a deep venous thromboembolism in the intervention group. Conclusions: A preoperative weight loss intervention using a dietitian and a mobile app was feasible and viewed favorably among patients. Remote dietitians and mobile apps may address gaps in access to obesity treatment before TJA. While the intervention subjects lost more weight and were more likely to achieve a BMI of <40 kg/m 2 , the differences were not significant. More intensive interventions may be needed to achieve enough weight loss for clinically important improvements in TJA. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Extramedullary multiple myeloma (EMM), defined in this review as soft tissue plasmacytomas resulting from hematogenous spread, is characterized by the ability of MM cells to proliferate outside of the bone marrow microenvironment. It is aggressive, often associated with high-risk cytogenetics and early relapse, and independently portends significantly shorter progression-free and overall survival, even in the era of highly effective immunotherapies. The molecular and microenvironmental factors underlying extramedullary MM dissemination continue to be studied to inform the development of better treatments. In this review, we discuss our current understanding of the biology of EMM, focusing on its distinct molecular and microenvironmental characteristics vis-à-vis MM. We also review the current treatment strategies, acknowledging the paucity of large, randomized studies specific to this population.

AbstractINTRODUCTIONAlzheimer's disease (AD) pathology causes corticobasal syndrome (CBS) in 21%–50% of patients. Studies have assessed hypometabolism in CBS according to β‐amyloid (A) positron emission tomography (PET), but the understanding of the association of both AD‐tau (T) and A with hypometabolism is incomplete.METHODSThirty‐three CBS patients and 45 controls underwent fluorodeoxyglucose (FDG), flortaucipir, and Pittsburgh compound‐B PET and were classified as A± and T±. FDG‐PET uptake was extracted for 12 regions‐of‐interest in dominant (most affected) and non‐dominant hemispheres and compared across A/T groups.RESULTSA+T+ patients had greater hypometabolism in temporo‐parieto‐occipital cortices than A+T‐ and A‐T‐ groups, with no differences observed between the A+T‐ and A‐T‐ groups. FDG asymmetry was more accentuated in A+T+ patients. Medial temporal and basal ganglia metabolism were similar across AT groups.DISCUSSIONAmyloid and tau positivity contribute synergistically to hypometabolism and asymmetry in temporo‐parieto‐occipital cortices in CBS, with AD‐like patterns of hypometabolism observed only in A+T+ patients.Highlights Amyloid (A) and tau PET (T) status can be used to stratify CBS patients. A+T+ CBS patients show more hypometabolism in temporo‐parieto‐occipital cortices. Medial temporal metabolism (typical AD pattern) is similar across AT groups. Parieto‐occipital cortices should be assessed when investigating AT pathology in CBS. Amyloid and tau positivity contribute synergistically to hypometabolism and asymmetry in CBS.

Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterised by multiorgan pathological histiocytic infiltration. Cardiac involvement occurs in 40–75% of patients and increases mortality. A 55-year-old woman with chest pain and dyspnoea was found to have an interatrial septal mass and aortitis suspicious for ECD without other organ involvement. After two inadequate transcatheter interatrial biopsies were obtained using ultrasound guidance alone, diagnostic samples were successfully obtained using intraprocedural frozen section examination. The patient started genotype-targeted treatment with good response. Biopsy confirmation of ECD is required to guide treatment; however, cardiac biopsies are uncommonly performed when other organs are affected. Our unique case of isolated cardiovascular involvement highlights how frozen sectioning with multimodal intraprocedural imaging guidance can improve diagnostic yield of endomyocardial biopsies. It also highlights how diagnosis of rare conditions requires careful multidisciplinary evaluation of affected organs, procedural risk and diagnostic yield. The use of frozen sectioning can improve diagnostic yield of endomyocardial biopsies.

The placenta is susceptible to infection by a number of viral pathogens, including severe acute respiratory syndrome coronavirus 2, which is associated with poor fetal outcomes. The histologic pattern of injury, termed severe acute respiratory syndrome coronavirus 2 placentitis, is characterized by a triad of increased perivillous fibrin deposition, intervillous histiocytes, and trophoblast necrosis. While the etiology of massive perivillous fibrin deposition (MPVFD) is mostly unknown, previous case reports of MPVFD in association with maternal Enterovirus (ENT) suggest that a subset of these cases are a consequence of undiagnosed viral infection. We evaluated 46 placentas collected between 2011 and 2022 with a diagnosis of MPVFD (n = 41) or chronic histiocytic intervillositis (CHI; n = 4). Combining methods of pan-viral metagenomic sequencing and targeted viral PCR, we detected Enterovirus DNA in 8 of 45 (18%) MPVFD and/or CHI cases. Seven of these positive cases were from MPVFD, and 1 was associated with a CHI diagnosis. Enterovirus A species (n = 7) were commonly identified, whereas one case had Enterovirus B. Histologic evaluation of these cases, including immunohistochemical staining for CD68, demonstrated increased intervillous histiocytes in Enterovirus-positive MPVFD cases in comparison with Enterovirus -negative, as well as evidence of trophoblast necrosis. Thus, we favor the terminology Enterovirus placentitis to describe this pathology. Overall, these findings suggest that Enterovirus is an underrecognized etiology of histologic MPVFD and, possibly, CHI. Further study to evaluate the recurrence risk of Enterovirus placentitis in comparison to MPVFD may help inform future fertility planning in patients with these diagnoses.

ABSTRACT Understanding lung cancer evolution can identify tools for intercepting its growth. In a landscape analysis of 1024 lung adenocarcinomas (LUAD) with deep whole-genome sequencing integrated with multiomic data, we identified 542 LUAD that displayed diverse clonal architecture. In this group, we observed an interplay between mobile elements, endogenous and exogenous mutational processes, distinct driver genes, and epidemiological features. Our results revealed divergent evolutionary trajectories based on tobacco smoking exposure, ancestry, and sex. LUAD from smokers showed an abundance of tobacco-related C:G>A:T driver mutations in KRAS plus short subclonal diversification. LUAD in never smokers showed early occurrence of copy number alterations and EGFR mutations associated with SBS5 and SBS40a mutational signatures. Tumors harboring EGFR mutations exhibited long latency, particularly in females of European-ancestry (EU_N). In EU_N, EGFR mutations preceded the occurrence of other driver genes, including TP53 and RBM10. Tumors from Asian never smokers showed a short clonal evolution and presented with heterogeneous repetitive patterns for the inferred mutational order. Importantly, we found that the mutational signature ID2 is a marker of a previously unrecognized mechanism for LUAD evolution. Tumors with ID2 showed short latency and high L1 retrotransposon activity linked to L1 promoter demethylation. These tumors exhibited an aggressive phenotype, characterized by increased genomic instability, elevated hypoxia scores, low burden of neoantigens, propensity to develop metastasis, and poor overall survival. Re-activated L1 retrotransposition-induced mutagenesis can contribute to the origin of the mutational signature ID2, including through the regulation of the transcriptional factor ZNF695 , a member of the KZFP family. The complex nature of LUAD evolution creates both challenges and opportunities for screening and treatment plans.

Abstract The development of targeted therapy for patients with multiple myeloma (MM) is hampered by the low frequency of actionable genetic abnormalities. Gain or amplification of chromosome 1q (1q+) is the most frequent arm-level copy number gain in patients with MM and is associated with higher risk of progression and death despite recent therapeutic advances. Thus, developing targeted therapy for patients with MM with 1q+ stands to benefit a large portion of patients in need of more effective management. Here, we used large-scale dependency screens and drug screens to systematically characterize the therapeutic vulnerabilities of MM with 1q+ and displayed increased sensitivity to myeloid cell leukemia-1 (MCL1) and phosphatidyl inositol 3-kinase (PI3K) inhibitors. Using single-cell RNA sequencing, we compared subclones with and without 1q+ within the same patient tumors and demonstrated that 1q+ is associated with higher levels of MCL1 and the PI3K pathway. Furthermore, by isolating isogenic clones with different copy number profiles for part of the chromosome 1q arm, we observed increased sensitivity to MCL1 and PI3K inhibitors with arm-level gain. Lastly, we demonstrated synergy between MCL1 and PI3K inhibitors and dissected their mechanism of action in MM with 1q+, uncovering a cytostatic effect. In conclusion, this study highlights that MM with 1q+ may present enhanced sensitivity to MCL1 and PI3K inhibitors, enabling their use at lower doses without sacrificing efficacy, and may thus accelerate the development of targeted therapy for patients with MM and 1q+.

Introduction Although osteosarcoma represents the most common primary malignant bone tumor in children, they comprise only 0.2% of all cancers. Osteosarcoma frequently involves long bones; however, 8% of osteosarcomas involve the skull or mandible. Osteosarcoma is generally categorized based on location within the bone (central, surface, or extraskeletal) and histological grade (high-grade or low-grade). Osteoblastic osteosarcoma is a central, high-grade subtype and may be difficult to diagnose; it may present similarly to osteoblastoma, another rare, but benign, type of osteoblastic bone tumor. In this report, we present a rare case of osteoblastic osteosarcoma involving the temporal-occipital skull. Study design Case report and systematic review. Setting Tertiary referral center. Results A 21-year-old male presented for assessment of a mass appearing over his left mastoid region, first noticed within the previous 12 months. He experienced growth of the lesion and pain that increased when pressure was applied to the mass. Results from fine needle aspiration and CT-guided core biopsy were positive for osteosarcoma, osteoblastic-type. Magnetic resonance imaging of the brain and skull base revealed the mass to be 2.8 cm in maximal diameter. Given a somewhat favorable location, the tumor could be completely excised en bloc with negative margins, and the patient subsequently received adjuvant chemotherapy. The patient is doing well at last follow-up 10 months after surgery, with no evidence of recurrence to date. Conclusion The temporal bone is an uncommon location for a primary osteosarcoma, and there are numerous conditions that could present in a similar manner. This case highlights this rare occurrence of osteoblastic osteosarcoma of the temporal bone without previous exposure to radiation. There are a limited number of similar cases in the literature, and our report serves to bring awareness to this potential diagnosis and considerations related to treatment.