Abstract In this study, we first analyzed data from 147 patients with solitary plasmacytomas treated at the Mayo Clinic between 2005 and 2022 and then expanded our investigation through a systematic review and meta-analysis of 62 studies, encompassing 3487 patients from the years 1960 to 2022. Our findings reveal that patients with up to 10% clonal plasma cells in their bone marrow (BM), denoted as plasmacytoma +, had a significantly reduced median disease-free survival (DFS) of 15.7 months vs 79 months, P < .05, observed in patients with true solitary plasmacytomas, with no clonal cells in the BM. Risk factors identified for shorter DFS included the presence of clonal plasma cells in the marrow and a difference between involved and uninvolved free light chains of >5 mg/dL. The meta-analysis portion of our study highlighted a male predominance among patients, with a median age of 58 years, and confirmed radiation therapy as the predominant treatment modality. We also found that DFS rates at 3, 5, and 10 years were 66.9%, 55%, and 42.1%, respectively, and noted a significant difference in outcomes between patients with bone and extramedullary plasmacytomas, with the latter group exhibiting better survival rates. This dual-faceted approach provides a thorough overview of survival rates and critical risk factors for patients with plasmacytoma, underscoring the vital role of accurate disease staging at diagnosis and the impact of tumor location on patient prognosis.
INSIDE-OUT: Introduction of Speakers at IDWeek Events—Observing for Unconscious Bias Over Time
Abstract Background Specialty societies, including the Infectious Diseases Society of America, strive to address gender and racial inequities in professional advancement. Microaggressions remain a persistent and pervasive barrier to these goals. Nonprofessional speaker introductions are a manifestation of race- and gender-based microaggressions, which have not been previously assessed at IDWeek. We assessed disparities in speaker introductions at IDWeek over a 7-year period that included formal gender equity initiatives introduced in 2016. Methods We conducted a retrospective observational study of video-recorded IDWeek speaker introductions from 2013 to 2019. Trained coders reviewed presentation video archives to assess a primary outcome of nonprofessional introductions: when a speaker's professional title was not used as the first introduction. We used descriptive statistics, Fisher exact tests, Cochrane-Armitage trend tests, and multivariable logistic regression to characterize relationships between speaker introductions and presentation year, speaker demographics, and speaker-moderator demographic concordance. Results Of 1940 videos reviewed, 48.9% of IDWeek speakers received nonprofessional introductions during and before 2016 vs 41.5% of speakers after 2016 (P = .0013). There was an increasing linear trend in the frequency of professional introductions by speaker age group from 47.1% for age <40 years to 65.3% for age >60 years (P < .0001). White moderators more frequently used nonprofessional introductions than moderators from backgrounds underrepresented in medicine (47.7% vs 29.1%, P = .0014). Women-men speaker-moderator pairs had more nonprofessional introductions (54.6%, P < .001). Conclusions In the largest assessment of microaggressions in speaker introductions at a national medical specialty conference, we highlighted some progress over time and ample opportunity to further standardize equitable speaker introductions, especially for women and junior speakers
Consensus Recommendations for the Management of Neurosarcoidosis
Objective Preclinical studies suggest that robotic carotid artery stenting (CAS) could be superior to manual CAS. However, very limited comparative data exists comparing robotic and manual CAS patients. In addition, no data exists comparing the costs of manual and robotic CAS. Methods All robotic CAS cases at 2 academic neurosurgery centers were retrospectively reviewed and 1:1 propensity matched with manual CAS cases. Personnel costs, supply costs, and total procedure costs were collected in collaboration with hospital administration using time‐driven activity‐based cost‐analysis (TDABC). Results 24 robotic CAS cases were performed between 2019 and 2023. Co‐morbidities and baseline procedural characteristics were well‐matched between robotic and manual cases. Unplanned manual conversion was observed in only one robotic case (4.2%). Robotic CAS complications and outcomes were comparable to manual. Robotic CAS was associated with a significantly increased fluoroscopy time (29.0 vs. 19.2 min.; p<0.001). Robotic procedure time (88.9±18.2 min.) was significantly (p=0.003) higher than manual (68.72±22.4 min.). Health professional costs ($1,589.71±176.92, $1,375.99±233.39, p<0.005), supply cost ($3,918.25±421.20, $2,152.74±1,030.26, p<0.001) and total procedure costs ($5,306.11±608.95, $3,437.56±1,165.67, p<0.001) were greater for robotic CAS. Conclusions With a low rate of technical failure and post‐operative complications, we show robotic carotid artery stenting is safe and feasible in the first multi‐center and largest sample to date. In addition, robotic CAS achieves comparable clinical outcomes. Robotic CAS was associated with increased fluoroscopy time, but fluoroscopy time decreased as operators gained familiarity with the CorPath GRX. Robotic CAS was associated with a greater procedural cost, which was driven by greater personnel and supply costs. Our findings highlight the need for further studies to optimize robotic CAS and reduce its associated costs.
Increase in white matter hyperintensities in long‐COVID depends on age and hospitalization during acute SARS‐CoV‐2
AbstractBackgroundApproximately 10% of patients with acute SARS‐CoV‐2 infection present with persistent symptoms recognized as the long‐COVID. Neurological and cognitive symptoms are prevalent in long‐COVID, requiring a deeper understanding of the biological basis of this condition for potential therapeutic interventions. Cerebrovascular complications are observed during acute infection, underscoring the importance of understanding cerebrovascular outcomes. Our objective was to investigate white matter hyperintensities (WMH) as a potential indicator of microvascular disease associated with long‐COVID in the brainMethodParticipants with long‐COVID (n=71; hospitalized, n=9, non‐hospitalized, n=62 during the acute infection) and controls (n=50) who did not have a reported infection were recruited from the community at five US sites that participated in the COVID‐Brain‐Advanced‐Imaging‐Network (COVID‐BRAIN) project. To be included, participants with long‐COVID had to experience neurological or cognitive sequelae within 6 months after a confirmed infection and continued to show at least one neurological symptom. Clinical evaluation and MRI were performed an average of 20±10 months after the acute infection. WMH volumes were measured from the 3D T2‐weighted FLAIR MRIs using a semi‐automated approach for the WMH segmentation. A linear regression model predicting log transformed WMH volume was used to investigate the association of age, groups (hospitalized long‐COVID, non‐hospitalized long‐COVID, controls), and the interaction of these two predictors along with an adjustment for total intracranial volume. Additionally, predicted regression lines have been plotted on the untransformed WMH scale.ResultWe observed a greater age‐dependent increase in WMH volumes in the hospitalized patients with long‐COVID compared to the control group (group*age interaction, p=0.005). We did not observe this difference in slopes in the non‐hospitalized patients with long‐COVID compared to the controls. Figure shows the slopes of WMH volume as a percentage of the total intracranial volume by age in the three groups.ConclusionOur preliminary observation in this ongoing long‐Covid study suggests that hospitalization during acute COVID is associated with the age‐dependent increase in microvascular injury in the white matter. Older adults with acute infection that require hospitalization are more susceptible to cerebrovascular adverse outcomes than controls or those who do not require hospitalization. Impact of such microvascular changes on cognitive outcomes and persistence of post‐COVID symptoms is yet to be studied.
Increase in white matter hyperintensities in long‐COVID depends on age and hospitalization during acute SARS‐CoV‐2
AbstractBackgroundApproximately 10% of patients with acute SARS‐CoV‐2 infection present with persistent symptoms recognized as the long‐COVID. Neurological and cognitive symptoms are prevalent in long‐COVID, requiring a deeper understanding of the biological basis of this condition for potential therapeutic interventions. Cerebrovascular complications are observed during acute infection, underscoring the importance of understanding cerebrovascular outcomes. Our objective was to investigate white matter hyperintensities (WMH) as a potential indicator of microvascular disease associated with long‐COVID in the brainMethodParticipants with long‐COVID (n = 71; hospitalized,n = 9,non‐hospitalized,n = 62 during the acute infection) and controls(n = 50) who did not have a reported infection were recruited from the community at five US sites that participated in the COVID‐Brain‐Advanced‐Imaging‐Network (COVID‐BRAIN) project. To be included, participants with long‐COVID had to experience neurological or cognitive sequelae within 6 months after a confirmed infection and continued to show at least one neurological symptom. Clinical evaluation and MRI were performed an average of 20±10 months after the acute infection. WMH volumes were measured from the 3D T2‐weighted FLAIR MRIs using a semi‐automated approach for the WMH segmentation. A linear regression model predicting log transformed WMH volume was used to investigate the association of age, groups (hospitalized long‐COVID, non‐hospitalized long‐COVID, controls), and the interaction of these two predictors along with an adjustment for total intracranial volume. Additionally, predicted regression lines have been plotted on the untransformed WMH scale.ResultWe observed a greater age‐dependent increase in WMH volumes in the hospitalized patients with long‐COVID compared to the control group (group*age interaction, p = 0.005). We did not observe this difference in slopes in the non‐hospitalized patients with long‐COVID compared to the controls. Figure shows the slopes of WMH volume as a percentage of the total intracranial volume by age in the three groups.ConclusionOur preliminary observation in this ongoing long‐Covid study suggests that hospitalization during acute COVID is associated with the age‐dependent increase in microvascular injury in the white matter. Older adults with acute infection that require hospitalization are more susceptible to cerebrovascular adverse outcomes than controls or those who do not require hospitalization. Impact of such microvascular changes on cognitive outcomes and persistence of post‐COVID symptoms is yet to be studied.
No Association Between Donor Variables and Clinically Significant Outcomes, Reoperations, and Failure After Osteochondral Allograft Transplantation
Background: Mismatch between osteochondral allograft (OCA) donor and recipient sex has been shown to negatively affect outcomes. This study accounts for additional donor variables and clinically relevant outcomes. Purpose: To evaluate whether donor sex, age, donor-recipient sex mismatch, and duration of graft storage affect clinical outcomes and failure rates after knee OCA transplantation. Study Design: Cohort study; Level of evidence, 3. Methods: Patients undergoing knee OCA transplantation between 2003 and 2018 were prospectively followed. Inclusion criteria consisted of primary OCA transplantation and minimum 2-year follow-up. Patient descriptive data and allograft donor sex, age, and graft storage time before implantation were collected. Patients were evaluated for reoperation, failure, and achievement of clinically significant outcomes for International Knee Documentation Committee scores. Reoperation was defined as subsequent surgical intervention of the transplanted allograft, including second-look arthroscopy for graft evaluation, debridement, and loose body removal. Failure was defined as revision of the primary OCA transplantation or conversion to arthroplasty. A Kaplan-Meier curve determined cumulative survivability of OCA transplantations, and log-rank testing was used to compare survivorship between groups. Stepwise regression analysis was utilized to evaluate associations between donor variables and achievement of clinically significant outcomes, reoperation, and failure. Results: A total of 372 patients undergoing OCA transplantation were included and followed for a mean 5.4 years (SD, 2.7; range, 2.0-16.3). Isolated OCA transplantation was performed in 45% of cases (169/372). A mismatch in donor and recipient sex was present for more female patients (90%) than male patients (10%; P < .001). Those who had a sex-mismatched graft more frequently underwent concomitant tibial tubercle osteotomy ( P = .034). When controlling for patient sex, no other differences were seen between groups matched and mismatched by sex. Univariable and multivariable analysis found no significant difference in survival free from reoperation or failure on the basis of donor-recipient sex mismatch, donor age, or graft storage time before implantation. Conclusion: In contrast to previous historical data, no donor variables were associated with inferior clinical outcomes in patients who underwent OCA transplantation. These data can help inform graft selection, expedient recipient selection, and outcome optimization after OCA transplantation.
The importance of Fcγ and C-type lectin receptors in host immune responses during
Pneumocystis
pneumonia
ABSTRACT Pneumocystis jirovecii pneumonia (PJP) remains a significant cause of morbidity and mortality during AIDS. In AIDS, the absence of CD4 immunity results in exuberant and often fatal PJP. In addition, organism clearance requires a balanced macrophage response since excessive inflammation promotes lung injury and respiratory failure. Corticosteroids given in addition to antibiotics significantly improve outcomes during PJP. However, concerns exist that corticosteroids further suppress immunity and increase co-infections. New strategies to promote killing and clearance of Pneumocystis while balancing lung inflammation are required. Prior studies have shown that innate immunity to Pneumocystis is mediated by C-type lectin receptors (CLRs) on macrophages and involves downstream CARD9 activation. CARD9 can be targeted by a novel specific small molecule inhibitor (BRD5529) that significantly reduces inflammatory signaling by macrophages. CARD9 serves as the central intracellular molecule through which Dectin-1, Dectin-2, Mincle, and other CLRs signal. Dectin-1 CLR is activated through its own intracytoplasmic domain, whereas other innate CLRs (e.g., Dectin-2 and Mincle) require interactions with a common Fc-gamma receptor (FcγR) accessory chain to mediate responses. We now observe that mice double deficient in both Dectin-1 and Fcer1g (which lack the FcγR gamma chain) exhibit markedly reduced organism clearance compared with Card9 −/− infected animals. These mice also possess deficiencies in immunoglobulin (Ig) Fc receptors directly mediating antibody responses, further implicating altered humoral responses in Pneumocystis killing. We further demonstrate in the Pneumocystis pneumonia (PCP) mouse model that BRD5529 administration successfully suppresses inflammatory cytokines. Our data support that innate immune responses through the CLR-CARD9 axis and humoral response act together to mediate effective responses resulting in optimal organism killing and generation of host inflammatory responses. Furthermore, host lung inflammation during PCP may be successfully reduced with a novel CARD9 small molecule inhibitor. IMPORTANCE Pneumocystis pneumonia (PCP) causes severe respiratory impairment in hosts with suppressed immunity, particularly those with CD4 deficiencies, such as HIV. In addition to lymphocytic immunity, both innate and humoral immunities also participate in host defense against Pneumocystis . In the current studies, we defined the relative roles of CLR receptor-mediated inflammation, as well as FcgR-related inflammation and clearance of Pneumocystis organisms. Our studies reveal important roles for CLR activities for inducing lung inflammation, which can be ameliorated with a novel small molecule inhibitor of the CARD9 adaptor protein that is necessary for CLR signaling. In contrast, FcgR has a dominant role in organism clearance, underscoring an integral role of humoral responses for the elimination of this infection.