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ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

Abstract Aims Invasive haemodynamic assessment with a pulmonary artery catheter is often used to guide the management of patients with cardiogenic shock (CS) and may provide important prognostic information. We aimed to assess prognostic associations and relationships to end-organ dysfunction of presenting haemodynamic parameters in CS. Methods and results The Critical Care Cardiology Trials Network is an investigator-initiated multicenter registry of cardiac intensive care units (CICUs) in North America coordinated by the TIMI Study Group. Patients with CS (2018–2022) who underwent invasive haemodynamic assessment within 24 h of CICU admission were included. Associations of haemodynamic parameters with in-hospital mortality were assessed using logistic regression, and associations with presenting serum lactate were assessed using least squares means regression. Sensitivity analyses were performed excluding patients on temporary mechanical circulatory support and adjusted for vasoactive-inotropic score. Among the 3603 admissions with CS, 1473 had haemodynamic data collected within 24 h of CICU admission. The median cardiac index was 1.9 (25th–75th percentile, 1.6–2.4) L/min/m2 and mean arterial pressure (MAP) was 74 (66–86) mmHg. Parameters associated with mortality included low MAP, low systolic blood pressure, low systemic vascular resistance, elevated right atrial pressure (RAP), elevated RAP/pulmonary capillary wedge pressure ratio, and low pulmonary artery pulsatility index. These associations were generally consistent when controlling for the intensity of background pharmacologic and mechanical haemodynamic support. These parameters were also associated with higher presenting serum lactate. Conclusion In a contemporary CS population, presenting haemodynamic parameters reflecting decreased systemic arterial tone and right ventricular dysfunction are associated with adverse outcomes and systemic hypoperfusion.

The NCCN Guidelines for Survivorship are intended to help healthcare professionals address the complex and varied needs of cancer survivors. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for psychosocial and physical problems resulting from adult-onset cancer and its treatment; recommendations to help promote healthy behaviors and immunizations in survivors; and a framework for care coordination. These NCCN Guidelines Insights summarize recent guideline updates and panel discussions pertaining to sleep disorders, fatigue, and cognitive function in cancer survivors.

Abstract Rationale In addition to rare genetic variants and the MUC5B locus, common genetic variants contribute to idiopathic pulmonary fibrosis (IPF) risk. The predictive power of common variants outside the MUC5B locus for IPF and interstitial lung abnormalities (ILAs) is unknown. Objectives We tested the predictive value of IPF polygenic risk scores (PRSs) with and without the MUC5B region on IPF, ILA, and ILA progression. Methods We developed PRSs that included (PRS-M5B) and excluded (PRS-NO-M5B) the MUC5B region (500-kb window around rs35705950-T) using an IPF genome-wide association study. We assessed PRS associations with area under the receiver operating characteristic curve (AUC) metrics for IPF, ILA, and ILA progression. Measurements and Main Results We included 14,650 participants (1,970 IPF; 1,068 ILA) from six multi-ancestry population-based and case–control cohorts. In cases excluded from genome-wide association study, the PRS-M5B (odds ratio [OR] per SD of the score, 3.1; P = 7.1 × 10−95) and PRS-NO-M5B (OR per SD, 2.8; P = 2.5 × 10−87) were associated with IPF. Participants in the top PRS-NO-M5B quintile had ∼sevenfold odds for IPF compared with those in the first quintile. A clinical model predicted IPF (AUC, 0.61); rs35705950-T and PRS-NO-M5B demonstrated higher AUCs (0.73 and 0.7, respectively), and adding both genetic predictors to a clinical model yielded the highest performance (AUC, 0.81). The PRS-NO-M5B was associated with ILA (OR, 1.25) and ILA progression (OR, 1.16) in European ancestry participants. Conclusions A common genetic variant risk score complements the MUC5B variant to identify individuals at high risk of interstitial lung abnormalities and pulmonary fibrosis.

Introduction: Stress echocardiography (SE) is a common functional imaging modality used for the detection of symptomatic coronary artery disease (CAD). Currently, the interpretation of SE relies on sex-based comparators for reporting parameters, including exercise time and functional aerobic capacity. These parameters are based on the cisgender male and female populations but have not been studied among transgender (TG) patients. Thus, we sought to characterize the SE parameters among a group of TG women. Methods: We designed a case-control study of TG women who underwent a SE at the Mayo Clinic. Each TG patient was age-matched with 2 cis-males and 2 cis-females. Demographics, medical history, and SE data were extracted. Conditional logistic regression analysis was performed to compare the TG cohort with each cisgender cohort separately. Results: Among the 43 TG females (age 57.7±9 years, 94.9% white), the prevalence of CAD was less than in cis-males (p=0.013) but similar to cis-females. For SE parameters, TG females had higher resting heart rates than cis-males (median [Q1, Q3]: 80 [71,93] vs 70 [64, 77]; p=0.002). Double product (24816 [21156, 27864] vs 26864 [22444, 30660]; p=0.016), exercise time (7.3 minutes [6,9] vs 8.5 [7.2, 9.5]; p=0.041), and metabolic equivalents (8.2 [7, 10] vs 9.5 [8.2, 10.5]; p=0.018), were all lower in TG females than cis-males. Exercise ejection fraction was higher in the transgender cohort than in cis-females (70 [70, 75] vs 70 [65, 70]; p=0.007). There was no difference in functional aerobic capacity or in the rest or stress wall motion score indices among the groups. Finally, there was no difference in the prevalence of positive electrocardiogram or SE studies. Conclusion: In conclusion, we report for the first time SE profiles for TG females which display an overall distinct phenotype compared to cis-males and cis-females. Larger prospective studies are warranted to further define these parameters for the TG population.

12114 Background: A retrospective study suggested a potential benefit from rose geranium in sesame oil nasal spray for alleviating nasal vestibulitis symptoms in patients (pts) undergoing chemotherapy. Methods: Pts undergoing active chemotherapy who reported moderate or worse nasal symptoms were randomized 1:1 to receive a rose geranium in sesame oil nasal spray (RG) or an isotonic saline nasal spray (IS), administered twice daily for two weeks. Consenting pts completed nasal symptom questionnaires at baseline and then weekly while on treatment. The number and percentage of pts experiencing improvements in their nasal symptoms 2 weeks after initiating the nasal spray, defined as symptoms moderately (2) or very much (3) better on a 7-point global impression of change score (ranging from scores of -3: very much worse, to 3: very much better), was estimated within and then between each randomized arm, using Fisher’s exact test (5% significance level). The estimated odds ratio was determined (95% confidence interval). After 2 weeks, pts initially randomized to IS were allowed to cross-over to RG and completed weekly surveys. Results: 106 pts consented to this study; 43 pts in the RG arm and 41 in the IS arm were evaluable for the primary endpoint. Pts had a mean age of 57.8 (SD 13.9). Demographic characteristics and baseline nasal symptoms were similar between arms. The most prominent baseline nasal symptoms were dryness (36%) and bleeding (35%). Of the 43 evaluable pts who received RG, 67.4% reported improved nasal symptoms, compared with 36.6% of the 41 pts who received IS (p=0.009; Table). On the global impression of change score, pts who received RG had a mean score of 1.93 (SD 1.16), compared to a mean score of 0.98 (SD 1.41) among pts who received IS. Adjusting for potential confounding factors, pts who received RG had a 4.56 odds of responding to the nasal spray, compared with those who received IS (p=0.005). There were no significant differences between pt responses based upon type of nasal symptoms, age, allergies, or gender. Adverse events were sparse and did not differ between arms. 34 pts crossed over to RG after week 2. Among the 29 pts who completed final surveys, 37% reported a response on IS, 79% reported a response on RG. Conclusions: Rose geranium in sesame oil nasal spray significantly improves nasal vestibulitis symptoms among patients undergoing chemotherapy. Clinical trial information: NCT04620369 . [Table: see text]

Myelin oligodendrocyte glycoprotein (MOG) antibody–associated disease (MOGAD) is an inflammatory demyelinating CNS condition characterized by the presence of MOG autoantibodies. We sought to investigate whether human MOG autoantibodies are capable of mediating damage to MOG-expressing cells through multiple mechanisms. We developed high-throughput assays to measure complement activity (CA), complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cellular cytotoxicity (ADCC) of live MOG-expressing cells. MOGAD patient sera effectively mediate all of these effector functions. Our collective analyses reveal that (a) cytotoxicity is not incumbent on MOG autoantibody quantity alone; (b) engagement of effector functions by MOGAD patient serum is bimodal, with some sera exhibiting cytotoxic capacity while others did not; (c) the magnitude of CDC and ADCP is elevated closer to relapse, while MOG-IgG binding is not; and (d) all IgG subclasses can damage MOG-expressing cells. Histopathology from a representative MOGAD case revealed congruence between lesion histology and serum CDC and ADCP, and we identified NK cells, mediators of ADCC, in the cerebrospinal fluid of relapsing patients with MOGAD. Thus, MOGAD-derived autoantibodies are cytotoxic to MOG-expressing cells through multiple mechanisms, and assays quantifying CDC and ADCP may prove to be effective tools for predicting risk of future relapses.